Podcasts about Merck

In his weekly clinical update, Dr. Griffin with Vincent Racaniello are alarmed at how RFK is breaking his promise of not altering vaccine policies, and nonexistent data and studies are used by members of the ACIP to make changes to immunization practices in the absence of a CDC director, justification for not honoring the US commitment to GAVI and global public policies including support of routine childhood immunizations, placing millions of children at risk for the return of vaccine preventable diseases including polio outbreaks in Pappa New Guinea and increased circulation of wildtype type 1 poliovirus, before Dr. Griffin reviews recent statistics on RSV, influenza and SARS-CoV-2 infections, the Wasterwater Scan dashboard, approval of Merck's anti-RSV mRNA monoclonal antibody, whether or not the NB.1.8.1 should be included in the fall 2025 vaccines, immunization recommendations for COVID-19 vaccines, where to find PEMGARDA, changes in COVID mRNA vaccine labeling and reframing of the science around the vaccine, provides information for Columbia University Irving Medical Center's long COVID treatment center, where to go for answers to your long COVID questions, and contacting your federal government representative to stop the assault on science and biomedical research Subscribe (free): Apple Podcasts, RSS, email Become a patron of TWiV! Links for this episode Jake Scott (Stanford University) Vaccine Randomized control trials (Bradspellberg.com) Vaccine RCT spreadsheet aims to show the data, dispel myths about vaccines  (CIDRAP) Vaccines-rcts (Bradspellberg.com) CDC's upcoming vaccine advisory meeting set up to sow distrust in vaccines (CIDRAP) Next ACIP meeting (CDC: ACIP) June meeting: MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) (CDC: ACIP agenda) Robert F Berman, PhD (UC Davis Health: Department of Neurological Surgery) Transparency = nonexistent data: CDC advisers appears to cite nonexistent study to support claims about risk of vaccine preservative (CNN) A C.D.C. Committee Just Voted Against Flu Shots With This Preservative. Is It Safe? (NY Times) CDC vaccine advisory committee to review long-approved immunizations (STAT News) Newly appointed CDC vaccine advisory committee holds first meeting, stirs more controversy (CIDRAP) FDA approves clesrovimab to protect infants during first RSV season (Contemporary Pediatrics) ACIP updates: Committee recommends clesrovimab for RSV, reaffirms routine influenza vaccination (Contemporary Pediatrics) Susan Monarez (Wikipedia) Robert F Kennedy Jr (Wikipedia) Centers for Disease Control and Prevention (Wikipedia) Who is in charge at the CDC (CDC: About CDC) Do children REALLY need to be vaccinated? (Wall Street Journal) U.S. Adults' Views on Routine Childhood Vaccination (Harvard Opinion Research Program) RFK Jr. declares US withdrawal from GAVI (YouTube) Kennedy Withdraws U.S. Funding Pledge to International Vaccine Agency (NY Times) Millions of children at risk as global vaccine rates fall (Guardian) Global, regional, and national trends in routine childhood vaccination coverage from 1980 to 2023 with forecasts to 2030 (LANCET) Polio this week: 47 WPV1 positive environmental samples this week! (GPEI) H5 bird flu: current situation (CDC: Avian Influenza) Cambodia logs fifth death from H5N1 avian flu as USDA weighs poultry vaccination (CIDRAP) Cambodia reports 6th H5N1 bird flu case this year(BNO News) USDA develops potential plan to vaccinate poultry for bird flu (Reuters) Wastewater for measles (WasterWater Scan) Measles cases and outbreaks (CDC Rubeola) Weekly measles and rubella monitoring (Government of Canada) Measles vaccine recommendations from NYP (jpg) Measles (WHO) Get the FACTS about measles (NY State Department of Health) Measles (CDC Measles (Rubeola)) Measles vaccine (CDC Measles (Rubeola)) Presumptive evidence of measles immunity (CDC) Contraindications and precautions to measles vaccination (CDC) Measles (CDC Measles (Rubeola)) Measles (CDC: Measles Rubeola) Adverse events associated with childhood vaccines: evidence bearing on causality (NLM) Measles Vaccination: Know the Facts(ISDA: Infectious Diseases Society of America) Deaths following vaccination: what does the evidence show (Vaccine) Influenza: Waste water scan for 11 pathogens (WastewaterSCan) US respiratory virus activity (CDC Respiratory Illnesses) Respiratory virus activity levels (CDC Respiratory Illnesses) Weekly surveillance report: clift notes (CDC FluView) FDA-CDC-DOD: 2025-2046 influenza vaccine composition (FDA) RSV: Waste water scan for 11 pathogens (WastewaterSCan) US respiratory virus activity (CDC Respiratory Illnesses) RSV-Network (CDC Respiratory Syncytial virus Infection) Novel Drug Approvals for 2025 (FDA) Waste water scan for 11 pathogens (WastewaterSCan) COVID-19 deaths (CDC) COVID-19 national and regional trends (CDC) COVID-19 variant tracker (CDC) SARS-CoV-2 genomes galore (Nextstrain) Antigenic and Virological Characteristics of SARS-CoV-2 Variant BA.3.2, XFG, and NB.1.8.1 (biRxiV) Episode 184: Fool's Gold: Reframing the Science…..reframing? (Apple Podcasts: Osterholm Update) Children with Post COVID-19 Multisystem Inflammatory Syndrome Display Unique Pathophysiological Metabolic Phenotypes (Journal of Proteome Research) FDA COVID mRNA vaccine labeling update (FDA) Where to get pemgarda (Pemgarda) EUA for the pre-exposure prophylaxis of COVID-19 (INVIYD) Infusion center (Prime Fusions) CDC Quarantine guidelines (CDC) NIH COVID-19 treatment guidelines (NIH) Drug interaction checker (University of Liverpool) Infectious Disease Society guidelines for treatment and management (ID Society) Molnupiravir safety and efficacy (JMV) Convalescent plasma recommendation for immunocompromised (ID Society) What to do when sick with a respiratory virus (CDC) Managing healthcare staffing shortages (CDC) Steroids,dexamethasone at the right time (OFID) Anticoagulation guidelines (hematology.org) Daniel Griffin's evidence based medical practices for long COVID (OFID) Long COVID hotline (Columbia : Columbia University Irving Medical Center) The answers: Long COVID Stellate Ganglion Block for the Treatment of COVID-19−Induced Parosmia (JAMA Otolaryngology-Head& Neck Surgery) Reaching out to US house representative Letters read on TWiV 1230 Dr. Griffin's COVID treatment summary (pdf) Timestamps by Jolene Ramsey. Thanks! Intro music is by Ronald Jenkees Send your questions for Dr. Griffin to daniel@microbe.tv Content in this podcast should not be construed as medical advice.

Today we look at some very basic management practices that data shows will increase the value of your calves when you go to market them.  The values has been derived from data through a partnership between Superior Livestock, Kansas State University, and Merck Animal Health.  So today Dr. Chris Thomsen with Merck joins us as he walks us through the data.  From breeding management to calfhood management, that also includes looking at the ROI on Precondition... what about Weaning? And what about the four things that DOESN'T affect the value of your calves?  Tune in to find out what those four things are and What Actually Pays a Net Premium on Your Calves! #workingranchmagazine #ranchlife #ranching #dayweather #weather #agweather #beef #cows #livestock #cattle #lowstress #k-line #RioMax #ManSaver #Gelbvieh #TankToad #Marketing #Weaning #Preconditioning #breeding

Dr. Diwakar Davar and Dr. Jason Luke discuss novel agents in melanoma and other promising new data in the field of immunotherapy that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Diwakar Davar: Hello. My name is Diwakar Davar, and I am welcoming you to the ASCO Daily News Podcast. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. Today, I'm joined by my colleague and good friend, Dr. Jason Luke. Dr. Luke is a professor of medicine. He is also the associate director of clinical research and the director of the Phase 1 IDDC Program at the University of Pittsburgh's Hillman Cancer Center. He and I are going to be discussing some key advancements in melanoma and skin cancers that were presented at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Jason, it is great to have you back on the podcast. Dr. Jason Luke: Thanks again so much for the opportunity, and I'm really looking forward to it. Dr. Diwakar Davar: Perfect. So we will go ahead and start talking a little bit about a couple of key abstracts in both the drug development immunotherapy space and the melanoma space. The first couple of abstracts, the first two, will cover melanoma. So, the first is LBA9500, which was essentially the primary results of RELATIVITY-098. RELATIVITY-098 was a phase 3 trial that compared nivolumab plus relatlimab in a fixed-dose combination against nivolumab alone for the adjuvant treatment of resected high-risk disease. Jason, do you want to maybe give us a brief context of what this is? Dr. Jason Luke: Yeah, it's great, thanks. So as almost all listeners, of course, will be aware, the use of anti–PD-1 immunotherapies really revolutionized melanoma oncology over the last 10 to 15 years. And it has become a standard of care in the adjuvant setting as well. But to review, in patients with stage III melanoma, treatment can be targeted towards BRAF with BRAF and MEK combination therapy, where that's relevant, or anti–PD-1 with nivolumab or pembrolizumab are a standard of care. And more recently, we've had the development of neoadjuvant approaches for palpable stage III disease. And in that space, if patients present, based on two different studies, either pembrolizumab or nivolumab plus ipilimumab can be given prior to surgery for somewhere in the 6- to 9-week range. And so all of these therapies have improved time-to-event endpoints, such as relapse-free or event-free survival. It's worth noting, however, that despite those advances, we've had a couple different trials now that have actually failed in this adjuvant setting, most high profile being the CheckMate-915 study, which looked at nivolumab plus ipilimumab and unfortunately was a negative study. So, with RELATIVITY-047, which was the trial of nivolumab plus relatlimab that showed an improvement in progression-free survival for metastatic disease, there's a lot of interest, and we've been awaiting these data for a long time for RELATIVITY-098, which, of course, is this adjuvant trial of LAG-3 blockade with relatlimab plus nivolumab. Dr. Diwakar Davar: Great. So with that, let's briefly discuss the trial design and the results. So this was a randomized, phase 3, blinded study, so double-blinded, so neither the investigators knew what the patients were getting, nor did the patients know what they were getting. The treatment investigational arm was nivolumab plus relatlimab in the fixed-dose combination. So that's the nivolumab standard fixed dose with relatlimab that was FDA approved in RELATIVITY-047. And the control arm was nivolumab by itself. The duration of treatment was 1 year. The patient population consisted of resected high-risk stage III or IV patients. The primary endpoint was investigator-assessed RFS. Stage and geography were the standard stratifying factors, and they were included, and most of the criteria were balanced across both arms. What we know at this point is that the 2-year RFS rate was 64% and 62% in the nivolumab and nivolumab-combination arms, respectively. The 2-year DMFS rate was similarly equivalent: 76% with nivolumab monotherapy, 73% with the combination. And similar to what you had talked about with CheckMate 915, unfortunately, the addition of LAG-3 did not appear to improve the RFS or DMFS compared to control in this patient population. So, tell us a little bit about your take on this and what do you think might be the reasons why this trial was negative? Dr. Jason Luke: It's really unfortunate that we have this negative phase 3 trial. There had been a lot of hope that the combination of nivolumab with relatlimab would be a better tolerated combination that increased the efficacy. So in the metastatic setting, we do have 047, the study that demonstrated nivolumab plus relatlimab, but now we have this negative trial in the adjuvant setting. And so as to why exactly, I think is a complicated scenario. You know, when we look at the hazard ratios for relapse-free survival, the primary endpoint, as well as the secondary endpoints for distant metastasis-free survival, we see that the hazard ratio is approximately 1. So there's basically no difference. And that really suggests that relatlimab in this setting had no impact whatsoever on therapeutic outcomes in terms of efficacy. Now, it's worth noting that there was a biomarker subanalysis that was presented in conjunction with these data that looked at some immunophenotyping, both from circulating T cells, CD8 T cells, as well as from the tumor microenvironment from patients who were treated, both in the previous metastatic trial, the RELATIVITY-047 study, and now in this adjuvant study in the RELATIVITY-098 study. And to briefly summarize those, what was identified was that T cells in advanced melanoma seemed to have higher expression levels of LAG-3 relative to T cells that are circulating in patients that are in the adjuvant setting. In addition to that, there was a suggestion that the magnitude of increase is greater in the advanced setting versus adjuvant. And the overall summary of this is that the suggested rationale for why this was a negative trial may have been that the target of LAG-3 is not expressed as highly in the adjuvant setting as it is in the metastatic setting. And so while the data that were presented, I think, support this kind of an idea, I am a little bit cautious that this is actually the reason for why the trial was negative, however. I would say we're not really sure yet as to why the trial was negative, but the fact that the hazard ratios for the major endpoints were essentially 1 suggests that there was no impact whatsoever from relatlimab. And this really makes one wonder whether or not building on anti–PD-1 in the adjuvant setting is feasible because anti–PD-1 works so well. You would think that even if the levels of LAG-3 expression were slightly different, you would have seen a trend in one direction or another by adding a second drug, relatlimab, in this scenario. So overall, I think it's an unfortunate circumstance that the trial is negative. Clearly there's going to be no role for relatlimab in the adjuvant setting. I think this really makes one wonder about the utility of LAG-3 blockade and how powerful it really can be. I think it's probably worth pointing out there's another adjuvant trial ongoing now of a different PD-1 and LAG-3 combination, and that's cemiplimab plus fianlimab, a LAG-3 antibody that's being dosed from another trial sponsor at a much higher dose, and perhaps that may make some level of difference. But certainly, these are unfortunate results that will not advance the field beyond where we were at already. Dr. Diwakar Davar: And to your point about third-generation checkpoint factors that were negative, I guess it's probably worth noting that a trial that you were involved with, KeyVibe-010, that evaluated the PD-1 TIGIT co-formulation of vibostolimab, MK-4280A, was also, unfortunately, similarly negative. So, to your point, it's not clear that all these third-generation receptors are necessarily going to have the same impact in the adjuvant setting, even if they, you know, for example, like TIGIT, and they sometimes may not even have an effect at all in the advanced cancer setting. So, we'll see what the HARMONY phase 3 trial, that's the Regeneron cemiplimab/fianlimab versus pembrolizumab control with cemiplimab with fianlimab at two different doses, we'll see how that reads out. But certainly, as you've said, LAG-3 does not, unfortunately, appear to have an impact in the adjuvant setting. So let's move on to LBA9501. This is the primary analysis of EORTC-2139-MG or the Columbus-AD trial. This was a randomized trial of encorafenib and binimetinib, which we will abbreviate as enco-bini going forward, compared to placebo in high-risk stage II setting in melanoma in patients with BRAF V600E or K mutant disease. So Jason, you know, you happen to know one or two things about the resected stage II setting, so maybe contextualize the stage II setting for us based on the trials that you've led, KEYNOTE-716, as well as CheckMate-76K, set us up to talk about Columbus-AD. Dr. Jason Luke: Thanks for that introduction, and certainly stage II disease has been something I've worked a lot on. The rationale for that has been that building off of the activity of anti–PD-1 in metastatic melanoma and then seeing the activity in stage III, like we just talked about, it was a curious circumstance that dating back about 7 to 8 years ago, there was no availability to use anti–PD-1 for high-risk stage II patients, even though the risk of recurrence and death from melanoma in the context of stage IIB and IIC melanoma is in fact similar or actually higher than in stage IIIA or IIIB, where anti–PD-1 was approved. And in that context, a couple of different trials that you alluded to, the Keynote-716 study that I led, as well as the CheckMate 76K trial, evaluated pembrolizumab and nivolumab, respectively, showing an improvement in relapse-free and distant metastasis-free survival, and both of those agents have subsequently been approved for use in the adjuvant setting by the US FDA as well as the European Medicines Agency.  So bringing then to this abstract, throughout melanoma oncology, we've seen that the impact of anti–PD-1 immunotherapy versus BRAF and MEK-targeted therapy have had very similar outcomes on a sort of comparison basis, both in frontline metastatic and then in adjuvant setting. So it was a totally reasonable question to ask: Could we use adjuvant BRAF and MEK inhibitor therapy? And I think all of us expected the answer would be yes. As we get into the discussion of the trial, I think the unfortunate circumstance was that the timing of this clinical trial being delayed somewhat, unfortunately, made it very difficult to accrue the trial, and so we're going to have to try to read through the tea leaves sort of, based on only a partially complete data set. Dr. Diwakar Davar: So, in terms of the results, they wanted to enroll 815 patients, they only enrolled 110. The RFS and DMFS were marginally improved in the treatment arm but certainly not significantly, which is not surprising because the trial had only accrued 16% to 18% of its complete accrual. As such, we really can't abstract from the stage III COMBI-AD data to stage II patients. And certainly in this setting, one would argue that the primary treatment options certainly remain either anti–PD-1 monotherapy, either with pembrolizumab or nivolumab, based on 716 or 76K, or potentially active surveillance for the patients who are not inclined to get treated.  Can you tell us a little bit about how you foresee drug development going forward in this space because, you know, for example, with HARMONY, certainly IIC disease is a part of HARMONY. We will know at least a little bit about that in this space. So what do you think about the stage IIB/C patient population? Is this a patient population in which future combinations are going to be helpful, and how would you think about where we can go forward from here? Dr. Jason Luke: It is an unfortunate circumstance that this trial could not be accrued at the pace that was necessary. I think all of us believe that the results would have been positive if they'd been able to accrue the trial. In the preliminary data set that they did disclose of that 110 patients, you know, it's clear there is a difference at a, you know, a landmark at a year. They showed a 16% difference, and that would be in line with what has been seen in stage III. And so, you know, I think it's really kind of too bad. There's really going to be no regulatory approach for this consideration. So using BRAF and MEK inhibition in stage II is not going to be part of standard practice moving into the future. To your point, though, about where will the field go? I think what we're already realizing is that in the adjuvant setting, we're really overtreating the total population. And so beyond merely staging by AJCC criteria, we need to move to biomarker selection to help inform which patients truly need the treatment. And in that regard, I don't think we've crystallized together as a field as yet, but the kinds of things that people are thinking about are the integration of molecular biomarkers like ctDNA. When it's positive, it can be very helpful, but in melanoma, we found that, unfortunately, the rates are quite low, you know, in the 10% to 15% range in the adjuvant setting. So then another consideration would be factors in the primary tumor, such as gene expression profiling or other considerations.  And so I think the future of adjuvant clinical trials will be an integration of both the standard AJCC staging system as well as some kind of overlaid molecular biomarker that helps to enrich for a higher-risk population of patients because on a high level, when you abstract out, it's just clearly the case that we're rather substantially overtreating the totality of the population, especially given that in all of our adjuvant studies to date for anti–PD-1, we have not yet shown that there's an overall survival advantage. And so some are even arguing perhaps we should even reserve treatment until patients progress. I think that's a complicated subject, and standard of care at this point is to offer adjuvant therapy, but certainly a lot more to do because many patients, you know, unfortunately, still do progress and move on to metastatic disease. Dr. Diwakar Davar: Let's transition to Abstract 2508. So we're moving on from the melanoma to the novel immunotherapy abstracts. And this is a very, very, very fascinating drug. It's IMA203. So Abstract 2508 is a phase 1 clinical update of IMA203. IMA203 is an autologous TCR-T construct targeting PRAME in patients with heavily pretreated PD-1-refractory metastatic melanoma. So Jason, in the PD-1 and CTLA-4-refractory settings, treatment options are either autologous TIL, response rate, you know, ballpark 29% to 31%, oncolytic viral therapy, RP1 with nivolumab, ORR about 30-ish percent. So new options are needed. Can you tell us a little bit about IMA203? Perhaps tell us for the audience, what is the difference between a TCR-T and traditional autologous TIL? And a little bit about this drug, IMA203, and how it distinguishes itself from the competing TIL products in the landscape. Dr. Jason Luke: I'm extremely enthusiastic about IMA203. I think that it really has transformative potential based on these results and hopefully from the phase 3 trial that's open to accrual now. So, what is IMA203? We said it's a TCR-T cell product. So what that means is that T cells are removed from a patient, and then they can be transduced through various technologies, but inserted into those T cells, we can then add a T-cell receptor that's very specific to a single antigen, and in this case, it's PRAME. So that then is contrasted quite a bit from the TIL process, which includes a surgical resection of a tumor where T cells are removed, but they're not specific necessarily to the cancer, and they're grown up in the lab and then given to the patient. They're both adoptive cell transfer products, but they're very different. One is genetically modified, and the other one is not. And so the process for generating a TCR-T cell is that patients are required to have a new biomarker that some may not be familiar with, which is HLA profiling. So the T-cell receptor requires matching to the concomitant HLA for which the peptide is bound in. And so the classic one that is used in most oncology practices is A*02:01 because approximately 48% of Caucasians have A*02:01, and the frequency of HLA in other ethnicities starts to become highly variable. But in patients who are identified to have A*02:01 genotype, we can then remove blood via leukapheresis or an apheresis product, and then insert via lentiviral transduction this T-cell receptor targeting PRAME. Patients are then brought back to the hospital where they can receive lymphodepleting chemotherapy and then receive the reinfusion of the TCR-T cells. Again, in contrast with the TIL process, however, these T cells are extremely potent, and we do not need to give high-dose interleukin-2, which is administered in the context of TIL. Given that process, we have this clinical trial in front of us now, and at ASCO, the update was from the phase 1 study, which was looking at IMA203 in an efficacy population of melanoma patients who were refractory at checkpoint blockade and actually multiple lines of therapy. So here, there were 33 patients and a response rate of approximately 50% was observed in this population of patients, notably with a duration of response approximately a year in that treatment group. And I realize that these were heavily pretreated patients who had a range of very high-risk features. And approximately half the population had uveal melanoma, which people may be aware is a generally speaking more difficult-to-treat subtype of melanoma that metastasizes to the liver, which again has been a site of resistance to cancer immunotherapy. So these results are extremely promising. To summarize them from what I said, it's easier to make TCR-T cells because we can remove blood from the patient to transduce the T cells, and we don't have to put them through surgery. We can then infuse them, and based on these results, it looks like the response rate to IMA203 is a little bit more than double what we expect from lifileucel. And then, whereas with lifileucel or TILs, we have to give high-dose IL-2, here we do not have to give high-dose IL-2. And so that's pretty promising. And a clinical trial is ongoing now called the SUPREME phase 3 clinical trial, which is hoping to validate these results in a randomized global study. Dr. Diwakar Davar: Now, one thing that I wanted to go over with you, because you know this trial particularly well, is what you think of the likelihood of success, and then we'll talk a little bit about the trial design. But in your mind, do you think that this is a trial that has got a reasonable likelihood of success, maybe even a high likelihood of success? And maybe let's contextualize that to say an alternative trial, such as, for example, the TebeAM trial, which is essentially a T-cell bispecific targeting GP100. It's being compared against SOC, investigator's choice control, also in a similarly heavily pretreated patient population. Dr. Jason Luke: So both trials, I think, have a strong chance of success. They are very different kinds of agents. And so the CD3 bispecific that you referred to, tebentafusp, likely has an effect of delaying progression, which in patients with advanced disease could have a value that might manifest as overall survival. With TCR-T cells, by contrast, we see a very high response rate with some of the patients going into very durable long-term benefit. And so I do think that the SUPREME clinical trial has a very high chance of success. It will be the first clinical trial in solid tumor oncology randomizing patients to receive a cell therapy as compared with a standard of care. And within that standard of care control arm, TILs are allowed as a treatment. And so it will also be the first study that will compare TCR-T cells against TILs in a randomized phase 3. But going back to the data that we've seen in the phase 1 trial, what we observe is that the duration of response is really connected to the quality of the response, meaning if you have more than a 50% tumor shrinkage, those patients do very, very well. But even in patients who have less than 50% tumor shrinkage, the median progression-free survival right now is about 4.5 months. And again, as we think about trial design, standard of care options for patients who are in this situation are unfortunately very bad. And the progression-free survival in that population is probably more like 2 months. So this is a trial that has a very high likelihood of being positive because the possibility of long-term response is there, but even for patients who don't get a durable response, they're likely going to benefit more than they would have based on standard chemotherapy or retreatment with an anti–PD-1 agent. Dr. Diwakar Davar: Really, a very important trial to enroll, a trial that is first in many ways. First of a new generation of TCR-T agents, first trial to look at cell therapy in the control arm, a new standard of efficacy, but potentially also if this trial is successful, it will also be a new standard of trial conduct, a new kind of trial, of a set of trials that will be done in the second-line immunotherapy-refractory space. So let's pivot to the last trial that we were going to discuss, which was Abstract 2501. Abstract 2501 is a first-in-human phase 1/2 trial evaluating BNT142, which is the first-in-class mRNA-encoded bispecific targeting Claudin-6 and CD3 in patients with Claudin-positive tumors. We'll talk a little bit about this, but maybe let's start by talking a little bit about Claudin-6. So Claudin-6 is a very interesting new target. It's a target that's highly expressed in GI and ovarian tumors. There are a whole plethora of Claudin-6-targeting agents, including T-cell bispecifics and Claudin-6-directed CAR-Ts that are being developed. But BNT142 is novel. It's a novel lipid nanoparticle LNP-encapsulated mRNA. The mRNA encodes an anti–Claudin-6 CD3 bispecific termed RiboMAB-021. And it then is administered to the patient. The BNT142-encoding mRNA LNPs are taken up by the liver and translated into the active drug. So Jason, tell us a little bit about this agent. Why you think it's novel, if you think it's novel, and let's talk a little bit then about the results. Dr. Jason Luke: So I certainly think this is a novel agent, and I think this is just the first of what will probably become a new paradigm in oncology drug development. And so you alluded to this, but just to rehash it quickly, the drug is encoded as genetic information that's placed in the lipid nanoparticle and then is infused into the patient. And after the lipid nanoparticles are taken up by the liver, which is the most common place that LNPs are usually taken up, that genetic material in the mRNA starts to be translated into the actual protein, and that protein is the drug. So this is in vivo generation, so the patient is making their own drug inside their body. I think it's a really, really interesting approach. So for any drug that could be encoded as a genetic sequence, and in this case, it's a bispecific, as you mentioned, CD3-Claudin-6 engager, this could have a tremendous impact on how we think about pharmacology and novel drug development moving into the future in oncology. So I think it's an extremely interesting drug, the like of which we'll probably see only more moving forward. Dr. Diwakar Davar: Let's maybe briefly talk about the results. You know, the patient population was heavily pretreated, 65 or so patients, mostly ovarian cancer. Two-thirds of the patients were ovarian cancer, the rest were germ cell and lung cancer patients. But let's talk a little bit about the efficacy. The disease control rate was about 58% in the phase 1 population as a whole, but 75% in the ovarian patient population. Now tell us a little bit about the interesting things about the drug in terms of the pharmacokinetics, and also then maybe we can pivot to the clinical activity by dose level. Dr. Jason Luke: Well, so they did present in their presentation at ASCO a proportionality showing that as higher doses were administered, that greater amounts of the drug were being made inside the patient. And so that's an interesting observation, and it's an important one, right? Suggesting that the pharmacology that we classically think of by administering drugs by IV, for example, would still be in play. And that did translate into some level of efficacy, particularly at the higher dose levels. Now, the caveat that I'll make a note of is that disease control rate is an endpoint that I think we have to be careful about because what that really means is sometimes a little bit unclear. Sometimes patients have slowly growing tumors and so on and so forth. And the clinical relevance of disease control, if it doesn't last at least 6 months, I think is probably pretty questionable. So I think these are extremely interesting data, and there's some preliminary sense that getting the dose up is going to matter because the treatment responses were mostly observed at the highest dose levels. There's also a caveat, however, that across the field of CD3 bispecific molecules like this, there's been quite a bit of heterogeneity in terms of the response rate, with some of them only really generating stable disease responses and other ones having more robust responses. And so I think this is a really interesting initial foray into this space. My best understanding is this molecule is not moving forward further after this, but I think that this really does set it up to be able to chase after multiple different drug targets on a CD3 bispecific backbone, both in ovarian cancer, but then basically across all of oncology. Dr. Diwakar Davar: Perfect. This is a very new sort of exciting arena where we're going to be looking at, in many ways, these programmable constructs, whether we're looking at in vivo-generated, in this case, a T-cell bispecific, but we've also got newer drugs where we are essentially giving drugs where people are generating in vivo CAR T, and also potentially even in vivo TCR-T. But certainly lots of new excitement around this entire class of drugs. And so, what we'd like to do at this point in time is switch to essentially the fact that we've got a very, very exciting set of data at ASCO 2025. You've heard from Dr. Luke regarding the advances in both early drug development but also in advanced cutaneous melanoma. And Jason, as always, thank you so much for sharing your very valuable and great, fantastic insights with us on the ASCO Daily News Podcast. Dr. Jason Luke: Well, thanks again for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for taking your time to listen today. You will find the links to the abstracts that we discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:    Dr. Diwakar Davar    @diwakardavar    Dr. Jason Luke @jasonlukemd Follow ASCO on social media:     @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn   Disclosures:     Dr. Diwakar Davar:      Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences     Consulting or Advisory Role: Instil Bio, Vedanta Biosciences     Consulting or Advisory Role (Immediate family member): Shionogi     Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences     Research Funding (Inst.): Zucero Therapeutics     Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy     Dr. Jason Luke:     Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX     Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine     Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure     Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)     Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Former FDA official Peter Marks criticized the agency's new risk-based COVID-19 vaccine framework, stating it contradicts the administration's transparency and science standards. The CDC's advisory committee recommended Merck's infant RSV vaccine, and Novavax's approval delay raised concerns about politicization of drug approval processes. Lilly's Verve deal revealed regulatory turmoil following Marks' resignation. Meanwhile, Trump's CDC pick supports vaccine safety, Novartis made a large bet on cardiovascular disease targets, and RFK cut US funding from vaccine alliance Gavi. The biopharma industry is hiring less international talent, and pharma companies face challenges with failed immuno-oncology projects. Evotec is hosting a webinar on preserving quality in the pharmaceutical industry.

David Faber and Jim Cramer discussed he AI boom helping to boost the tech rally. Nvidia hitting a new all-time and surpassing Microsoft to become the world's most valuable company. Micron CEO Sanjay Mehrotra joined the program exclusively to discuss the role AI played in the chipmaker's better-than-expected earnings and upbeat guidance. Also in focus: Microsoft and Meta go after OpenAl for different reasons, Tesla vs. Waymo on robotaxis, McCormick's spicy earnings, Q1 GDP shrinks more than expected, RFK Jr.'s vaccine panel backs Merck's RSV shot for infants, Cramer's message on skyrocketing stocks and the "FOMO" trade. Squawk on the Street Disclaimer

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss important advances in the treatment of prostate, bladder, and kidney cancers that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute and editor-in-chief of the ASCO Daily News.  I am delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of the GU Center at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that were presented at the 2025 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode.  Jeanny, it is great to have you on the podcast. Dr. Jeanny Aragon-Ching: Oh, thank you so much, Neeraj. Dr. Neeraj Agarwal: Jeanny, let's begin with some prostate cancer abstracts. Let's begin with Abstract 5017 titled, “Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer.” Can you walk us through the design and the key findings of this first-in-human trial? Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So this study, presented by Dr. Capucine Baldini, introduces pasritamig, a first-in-class T-cell redirecting bispecific antibody that simultaneously binds KLK2 on prostate cancer cells and CD3 receptor complexes on T cells. KLK2 is also known as human kallikrein 2, which is selectively expressed in prostate tissue. And for reference, KLK3 is what we now know as the PSA, prostate-specific antigen, therefore making it an attractive and specific target for therapeutic engagement. Now, while this was an early, first-in-human, phase 1 study, it enrolled 174 heavily pretreated metastatic CRPC patients. So many were previously treated with ARPIs, taxanes, and radioligand therapy. So given the phase 1 nature of this study, the primary objective was to determine the safety and the RP2D, which is the recommended phase 2 dose. Secondary objectives included preliminary assessment of antitumor activity. So, pasritamig was generally well tolerated. There were no treatment-related deaths. Serious adverse events were rare. And in the RP2D safety cohort, where patients received the step-up dosing up to 300 mg of IV every 6 weeks, the most common treatment-related adverse events were low-grade infusion reactions. There was fatigue and grade 1 cytokine release syndrome, what we call CRS. And no cases of neurotoxicity, or what we call ICANS, the immune effector cell-associated neurotoxicity syndrome, reported. Importantly, the CRS occurred in just about 8.9% of patients. All were grade 1. No patients required tocilizumab or discontinued treatment due to adverse events. So, this suggests a favorable safety profile, allowing hopefully for outpatient administration without hospitalization, which will be very important when we're thinking about bispecifics moving forward. In terms of efficacy, pasritamig showed promising activity. About 42.4% of evaluable patients achieved a PSA50 response. Radiographic PFS was about 6.8 months. And among patients with measurable disease, the objective response rate was about 16.1% in those with lymph node or bone metastases, and about 3.7% in those with visceral disease, with a median duration of response of about 11.3 months. So, altogether, this data suggests that pasritamig may offer a well-tolerated and active new potential option for patients with metastatic CRPC.   Again, as a reminder, with the caveat that this is still an early phase 1 study. Dr. Neeraj Agarwal: Thank you, Jeanny. These are promising results for a bispecific T-cell engager, pasritamig, in prostate cancer. I agree, the safety and durability observed here stand out, and this opens the door for further development, possibly even in earlier disease settings.  So, shifting now from immunotherapy to the evolving role of genomics in prostate cancer. So let's discuss Abstract 5094, a real-world, retrospective analysis exploring the prognostic impact of homologous recombination repair gene mutations, especially BRCA1 and BRCA2 mutations, in metastatic hormone-sensitive prostate cancer. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So this study was presented by Dr. David Olmos, represents one of the largest real-world analyses we have evaluating the impact of homologous recombination repair, or what we would call HRR, alterations in metastatic hormone-sensitive prostate cancer. So, this cohort included 556 men who underwent paired germline and somatic testing. Now, about 30% of patients had HRR alterations, with about 12% harboring BRCA1 or BRCA2 mutations and 16% having alterations in other HRR genes. Importantly, patients were stratified via CHAARTED disease volume, and outcomes were examined across treatment approaches, including ADT alone, doublet therapy, and triplet therapy. The prevalence of BRCA and HRR alterations were about similar between the metastatic hormone-sensitive prostate cancer and the metastatic castrate-resistant prostate cancer, with no differences observed, actually, between the patients with high volume versus low volume disease.  So, the key finding was that BRCA and HRR alterations were associated with poor clinical outcomes in metastatic hormone-sensitive prostate cancer. And notably, the impact of these alterations may actually be even greater in metastatic hormone-sensitive prostate cancer than previously reported in metastatic CRPC. So, the data showed that when BRCA mutations are present, the impact of the volume of disease is actually limited. So, poor outcomes were observed across the board for both high-volume and low-volume groups. So, the analysis showed that patients with HRR alterations had significantly worse outcomes compared to patients without HRR alterations. Median radiographic progression-free survival was about 20.5 months for the HRR-altered patients versus 30.6 months for the non-HRR patients, with a hazard ratio of 1.6. Median overall survival was 39 months for HRR-altered patients compared to 55.7 months for the non-HRR patients, with a hazard ratio of 1.5. Similar significant differences were observed when BRCA-mutant patients were compared with patients harboring non-BRCA HRR mutations. Overall, poor outcomes were independent of treatment of ARPI or taxanes. Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data reinforce homologous recombination repair mutations as both a predictive and prognostic biomarker, not only in the mCRPC, but also in the metastatic hormone-sensitive setting as well. It also makes a strong case for incorporating genomic testing early in the disease course and not waiting until our patients have castration-resistant disease. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. And I think this really brings home the point and the lead up to the AMPLITUDE trial, which is LBA5006, a phase 3 trial that builds on this very concept of testing with a PARP inhibitor, niraparib, in the hormone-sensitive space. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the AMPLITUDE trial, a phase 3 trial presented by Dr. Gerhardt Attard, enrolled 696 patients with metastatic hormone-sensitive prostate cancer and HRR gene alterations. 56% of these patients had BRCA1 and BRCA2 mutations. Patients were randomized to receive abiraterone with or without niraparib, a PARP inhibitor. The majority of patients, 78% of these patients, had high-volume metastatic hormone-sensitive prostate cancer, and 87% of these patients had de novo metastatic HSPC. And 16% of these patients received prior docetaxel, which was allowed in the clinical trial. So, with a median follow-up of nearly 31 months, radiographic progression-free survival was significantly prolonged with the niraparib plus abiraterone combination, and median was not reached in this arm, compared to abiraterone alone, which was 29.5 months, with a hazard ratio of 0.63, translating to a 37% reduction in risk of progression or death. This benefit was even more pronounced in the BRCA1 and BRCA2 subgroup, with a 48% reduction in risk of progression, with a hazard ratio of 0.52. Time to symptomatic progression also improved significantly across all patients, including patients with BRCA1, BRCA2, and HRR mutations. Although overall survival data remain immature, early trends favored the niraparib plus abiraterone combination. The safety profile was consistent with prior PARP inhibitor studies, with grade 3 or higher anemia and hypertension were more common but manageable. Treatment discontinuation due to adverse events remained low at 11%, suggesting that timely dose modifications when our patients experience grade 3 side effects may allow our patients to continue treatment without discontinuation. These findings support niraparib plus abiraterone as a potential new standard of care in our patients with metastatic hormone-sensitive prostate cancer with HRR alterations, and especially in those who had BRCA1 and BRCA2 mutations. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. This trial is especially exciting because it brings PARP inhibitors earlier into the treatment paradigm. Dr. Neeraj Agarwal: Exactly. And it is exciting to see the effect of PARP inhibitors in the earlier setting.  So Jeanny, now let's switch gears a bit to bladder cancer, which also saw several impactful studies. Could you tell us about Abstract 4502, an exploratory analysis from the EV-302 trial, which led to approval of enfortumab vedotin plus pembrolizumab for our patients with newly diagnosed metastatic bladder cancer? So here, the authors looked at the outcomes in patients who achieved a confirmed complete response with EV plus pembrolizumab. Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, EV-302 demonstrated significant improvements in progression-free and overall survival for patients previously treated locally advanced or metastatic urothelial cancer, I'll just call it metastatic UC, as a frontline strategy, establishing EV, which is enfortumab vedotin, plus pembro, with pembrolizumab as standard of care in this setting.  So, this year at ASCO, Dr Shilpa Gupta presented this exploratory responder analysis from the phase 3 EV-302 trial. Among 886 randomized patients, about 30.4% of patients, this is about 133, in the EV+P arm, and 14.5% of the patients in the chemotherapy arm, achieved a confirmed complete response. They call it the CCR rates. So for patients who achieved this, median PFS was not reached with EV+P compared to 26.9 months with chemotherapy, with a hazard ratio of 0.36, translating to a 64% reduction in the risk of progression. Overall survival was also improved. So the median OS was not reached in either arm, but the hazard ratio favored the EV+P at 0.37, translating to a 63% reduction in the risk of death. The median duration of complete response was not reached with EV+P compared to 15.2 months with chemotherapy. And among those patients who had confirmed CRs at 24 months, 78% of patients with the EV+P arm remained progression-free, and around 95% of the patients were alive, compared to 54% of patients who were progression-free and 86% alive of the patients in the chemotherapy arm. Safety among responders were also consistent with prior reports. Grade 3 or higher treatment-related adverse events occurred in 62% of EV+P responders and 72% of chemotherapy responders. Most adverse events were managed with dose modifications, and importantly, no treatment-related deaths were reported among those who were able to achieve complete response.  So these findings further reinforce EV and pembro as the preferred first-line therapy for metastatic urothelial carcinoma, offering a higher likelihood of deep, durable responses with a fairly manageable safety profile. Dr. Neeraj Agarwal: Thank you for the great summary, Jeanny. These findings underscore the depth and durability of responses achievable with this combination and also suggest that achieving a response may be a surrogate for long-term benefit in patients with metastatic urothelial carcinoma.  So now, let's move to Abstract 4503, an exploratory ctDNA analysis from the NIAGARA trial, which evaluated perioperative durvalumab, an immune checkpoint inhibitor, in muscle-invasive bladder cancer. So what can you tell us about this abstract? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, in NIAGARA, presented by Dr. Tom Powles, the addition of perioperative durvalumab to neoadjuvant chemotherapy, gem/cis, significantly improved event-free survival, overall survival, and pathologic complete response in patients with cisplatin-eligible muscle-invasive bladder cancer. Recall that this led to the U.S. FDA approval of this treatment regimen on March 28, 2025.  So, a planned exploratory analysis evaluated the ctDNA dynamics and their association with clinical outcomes, which was the one presented recently at ASCO. So, the study found that the incidence of finding ctDNA positivity in these patients was about 57%. Following neoadjuvant treatment, this dropped to about 22%, with ctDNA clearance being more common in the durvalumab arm, about 41%, compared to the chemotherapy control arm of 31%. Notably, 97% of patients who remained ctDNA positive prior to surgery failed to achieve a pathologic CR. So, this indicates a strong association between ctDNA persistence and lack of tumor eradication. So, postoperatively, only about 9% of patients were ctDNA positive. So, importantly, durvalumab conferred an event-free survival benefit regardless of ctDNA status at both baseline and post-surgery. Among patients who were ctDNA positive at baseline, durvalumab led to a hazard ratio of 0.73 for EFS. So, this translates to a 27% reduction in the risk of disease recurrence, progression, or death compared to the control arm. In the post-surgical ctDNA-positive group, the disease-free survival was also improved with a hazard ratio of 0.49, translating to a 51% reduction in the risk of recurrence.  So, these findings underscore the prognostic value of ctDNA and suggest that durvalumab provides clinical benefit irrespective of molecular residual disease status. So, the data also supports that ctDNA is a promising biomarker for future personalized strategies in the perioperative treatment of muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Thank you, Jeanny. It is great to see that durvalumab is improving outcomes in these patients regardless of ctDNA status. However, based on these data, presence of ctDNA in our patients warrants a closer follow-up with imaging studies, because these patients with positive ctDNA seem to have a higher risk of recurrence. Dr. Jeanny Aragon-Ching: I agree, Neeraj.  Let's round out the bladder cancer discussion with Abstract 4518, which reported the interim results of SURE-02, which is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab in cisplatin-ineligible muscle-invasive bladder cancer. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure, Jeanny. So, Dr Andrea Necchi presented interim results from the SURE-02 trial. This is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by a response-adapted bladder-sparing treatment and adjuvant pembrolizumab in patients with muscle-invasive bladder cancer.  So, in this interim analysis, 40 patients were treated and 31 patients were evaluable for efficacy. So, the clinical complete response rate was 38.7%. All patients achieving clinical complete response underwent bladder-sparing approach with a repeat TURBT instead of radical cystectomy. Additionally, 51.6% of patients achieved excellent pathologic response with a T stage of 1 or less after neoadjuvant therapy. The treatment was well tolerated, with only 12.9% of patients experiencing grade 3 or higher adverse events without needing dose reduction of sacituzumab. Molecular profiling, interestingly, showed that clinical complete response correlated with luminal and genomically unstable subtypes, while high stromal gene expression was associated with lack of response.  These results suggest that sacituzumab plus pembrolizumab combination has promising activity in this setting, and tolerability, and along with other factors may potentially allow a bladder preservation approach in a substantial number of patients down the line. Dr. Jeanny Aragon-Ching: Yeah, agree with you, Neeraj. And the findings are very provocative and support completing the full trial enrollment and further exploration of this strategy in muscle-invasive bladder cancer in order to improve and provide further bladder-sparing strategies. Dr. Neeraj Agarwal: Agree. So, let's now turn to the kidney cancer, starting with Abstract 4505, the final overall analysis from CheckMate-214 trial, which evaluated nivolumab plus ipilimumab, so dual checkpoint inhibition strategy, versus sunitinib in our patients with metastatic clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So, the final 9-year analysis of the phase 3 CheckMate-214 trial confirms the long-term superiority of nivolumab and ipilimumab over sunitinib for first-line treatment of advanced metastatic renal cell carcinoma. So, this has a median follow-up of 9 years. Overall survival remains significantly improved with the combination. So, in the ITT patient population, the intention-to-treat, the hazard ratio for overall survival was 0.71. So, this translates to a 29% reduction in the risk of death. 31% of patients were alive at this 108-month follow-up compared to 20% only in those who got sunitinib. So, similar benefits were observed in the intermediate- and poor-risk groups with a hazard ratio of 0.69, and 30% versus 19% survival at 108 months.  Importantly, a delayed benefit was also seen in those favorable-risk patients. So, the hazard ratio for overall survival improved from 1.45 in the initial report and now at 0.8 at 9 years follow-up, with 35% of patients alive at 108 months compared to 22% in those who got sunitinib. Progression-free survival also favored the nivo-ipi arm across all risk groups. At 96 months, the probability of remaining progression-free was about 23% compared to 9% in the sunitinib arm in the ITT patient population, 25% versus 9% in the intermediate- and poor-risk patients, and 13% compared to 11% in the favorable-risk patients. Importantly, at 96 months, 48% of patients in the nivo-ipi responders remained in response compared to just 19% in those who got sunitinib. And in the favorable-risk group, 36% of patients who responded remained in response, although data were not available for sunitinib in this subgroup.  So, this data reinforces the use of nivolumab and ipilimumab as a durable and effective first-line effective strategy for standard of care across all risk groups for advanced renal cell carcinoma. Dr. Neeraj Agarwal: Thank you, Jeanny. And of course, since ipi-nivo data were presented, several other novel ICI-TKI combinations have emerged. And I'm really hoping to see very similar data with TKI-ICI combinations down the line. It is really important to note that we are not seeing any new safety signals with the ICI combinations or ICI-based therapies, which is very reassuring given the extended exposure. Dr. Jeanny Aragon-Ching: Absolutely agree with you there, Neeraj.  Now, going on and moving on to Abstract 4514, which is the KEYNOTE-564 trial, and they reported on the 5-year outcomes of adjuvant pembrolizumab in clear cell RCC in patients who are at high risk for recurrence. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the KEYNOTE-564 trial established pembrolizumab monotherapy as the first adjuvant regimen to significantly improve both disease-free survival and overall survival compared to placebo after surgery for patients with clear cell renal cell carcinoma. So, Dr Naomi Haas presented the 5-year update from this landmark trial.  A total of 994 patients were randomized to receive either pembrolizumab or placebo. The median follow-up at the time of this analysis was approximately 70 months. Disease-free survival remained significantly improved with pembrolizumab. The median DFS was not reached with pembrolizumab compared to 68.3 months with placebo, with a hazard ratio of 0.71, translating to a 29% reduction in risk of recurrence. At 5 years, 60.9% of patients receiving pembrolizumab remained disease-free compared to 52.2% with placebo. Overall survival also favored pembrolizumab. The hazard ratio for OS was 0.66, translating to a 34% reduction in risk of death, with an estimated 5-year overall survival rate of 87.7% with pembrolizumab compared to 82.3% for placebo. Importantly, these benefits were consistent across all key subgroups, including patients with sarcomatoid features. In addition, no new serious treatment-related adverse events have been reported in the 3 years since treatment completion.  So, these long-term data confirm pembrolizumab as a durable and effective standard adjuvant therapy for patients with resected, high-risk clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Thank you for that wonderful summary, Neeraj. Dr. Neeraj Agarwal: That wraps up our kidney cancer highlights. Any closing thoughts, Jeanny, before we conclude? Dr. Jeanny Aragon-Ching: It's been so wonderful reviewing these abstracts with you, Neeraj. So, the 2025 ASCO Annual Meeting showcased a lot of transformative data across GU cancers, from first-in-class bispecifics to long-term survival in RCC. And these findings are already shaping our clinical practices. Dr. Neeraj Agarwal: I agree. And we have covered a broad spectrum of innovations in GU cancers with strong clinical relevance.  So, thank you, Jeanny, for joining me today and sharing your insights.  And thank you to our listeners for joining us. You will find links to the abstracts discussed today in the transcript of this episode. If you find these conversations valuable, please take a moment to rate, review, and subscribe to the ASCO Daily News Podcast wherever you listen. Thank you so much. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:    Dr. Neeraj Agarwal     @neerajaiims     Dr. Jeanny Aragon-Ching   Follow ASCO on social media:       @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn       Disclosures:   Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas  Dr. Jeanny Aragon-Ching:   Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono   Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,    Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics

In this podcast episode, Miguel Regueiro, MD, discusses developing the medical home model for patients with IBD, technological advances for patients in GI and more. •    Intro :58 •    The interview/about Regueiro 1:03 •    Tell us about your family and where you grew up. 1:24 •    How did you get interested in medicine? 2:16 •    Who were your early influences?  4:18 •    What is the medical home? 5:57 •    How did you develop the idea to apply the medical home model to IBD? 7:45 •    Did you get any funding from the payers for this model to keep costs under control for this patient population? 10:57 •    Why hasn't this model become standard of care for patients with complex IBD? 14:13 •    What has worked, and what hasn't worked when it comes to adopting an integrative care medical home model? 18:15 •    Are there themes patients share as to why they wouldn't want to be enrolled in a medical home? 21:28 •    What motivated your change to go from UPMC to become the GI Chief of Cleveland Clinic? 23:09 •    What have you learned in this position at Cleveland Clinic? 25:23 •    Are you spending a lot of time on the business side of care as opposed to the patient side? 26:34 •    How would you recommend that people prepare for having a position like this? 27:34 •    Are you seeing a shift in excitement over taking on leadership roles outside of traditional academics? 30:02 •    With our clinical tool chest changing so rapidly, is there a common theme that you use to guide the strategy of the institute on what to invest in? 35:06 •    What are the challenges that you still see in the ways we are using telehealth? 39:05 •    What are some of the most exciting things you see on the horizon in the realm of IBD management? 40:26 •    Thank you, Miguel 42:55 •    Thanks for listening 45:11 Miguel Regueiro, MD, is the chief of the Digestive Disease Institute at Cleveland Clinic, and professor in the department of medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. We'd love to hear from you! Send your comments/questions to guttalkpodcast@healio.com. Follow us on X @HealioGastro @sameerkberry @umfoodoc. For more from Regueiro, follow @MRegueiroMD on X. Disclosures: Berry and Chey report no relevant financial disclosures. Regueiro reports being on the advisory boards of and consulting for Abavax, Abbvie, Amgen, Biocon, BMS, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celgene, Celltrion, Gilead, Genentech, Johnson and Johnson, Lilly, Merck, Organon, Pfizer, Prometheus, Roche, Salix, Sanofi, Takeda and UBC.

Dr. Vamsi Velcheti and Dr. Nate Pennell discuss novel treatment approaches in small cell and non-small cell lung cancer that were featured at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host of the ASCO Daily News Podcast. I'm a professor of medicine and chief of hematology and oncology at the Mayo Clinic in Jacksonville, Florida. The 2025 ASCO Annual Meeting featured some exciting advancements in small cell lung cancer, targeted therapies for non-small cell lung cancer, and other novel [treatment] approaches. Today, I'm delighted to be joined by Dr. Nate Pennell to discuss some of the key abstracts that are advancing the lung cancer field. Dr. Pennell is the co-director of the Cleveland Clinic Lung Cancer Program and also the vice chair of clinical research at the Taussig Cancer Institute. Our full disclosures are available in the transcript of this episode. Nate, it's great to have you back on the podcast. Thanks so much for being here. Dr. Nate Pennell: Thanks, Vamsi. Always a pleasure. Dr. Vamsi Velcheti: Let's get started, and I think the first abstract that really caught my attention was Abstract 8516, “The Randomized Trial of Relevance of Time of Day of Immunotherapy for Progression-Free and Overall Survival in Patients With Non-Small Cell Lung Cancer.” What are your thoughts about this, Nate? Dr. Nate Pennell: I agree. I thought this was one of the most discussed abstracts, certainly in the lung cancer session, but I think even outside of lung cancer, it got some discussion. So, just to put this in perspective, there have been a number of publications that have all been remarkably consistent, and not just in lung cancer but across multiple cancer types, that immunotherapy, immune checkpoint inhibitors, are commonly used. And all of them have suggested, when looking at retrospective cohorts, that patients who receive immune checkpoint inhibitors earlier in the day – so in the morning or before the early afternoon – for whatever reason, appear to have better outcomes than those who get it later in the day, and this has been repeated. And I think many people just sort of assumed that this was some sort of strange association and that there was something fundamentally different from a prognostic standpoint in people who came in in the morning to get their treatment versus those who came later in the afternoon, and that was probably the explanation. The authors of this randomized trial actually decided to test this concept. And so, about 210 patients with previously untreated advanced non-small cell lung cancer were randomly assigned to get chemo and immune checkpoint inhibitor – either pembrolizumab or sintilimab – and half of them were randomly assigned to get the treatment before 3 PM in the afternoon, and half of them were assigned to get it after 3 PM in the afternoon. And it almost completely recapitulated what was seen in the retrospective cohorts. So, the median progression-free survival in those who got earlier treatment was 13.2 months versus only 6.5 months in those who got it later in the day. So, really enormous difference with a hazard ratio of 0.43, which was statistically significant. And perhaps even more striking, the median overall survival was not reached in the early group versus 17.8 months in the late group with a hazard ratio of 0.43, also highly statistically significant. Even the response rate was 20% higher in the early patients; 75% response rate compared to 56% in the late-time-of-day patients. So very consistent across all measures of efficacy with pretty good matched characteristics across the different groups. And so, I have to tell you, I don't know what to make of this. I certainly was a skeptic about the retrospective series, but now we have a prospective randomized trial that shows essentially the same thing. So, maybe there is a difference between getting treated in the morning, although I have yet to hear someone give a very good mechanistic explanation as to why this would be. What were your thoughts on this? Dr. Vamsi Velcheti: It's indeed fascinating, Nate, and I actually think this was a very interesting abstract. Really, I was caught off guard looking at the data. I mean, if it were a drug, we would be so excited, right? I mean, with those kind of survival benefits. I don't know. I think circadian rhythm probably has something to do with it, like different cytokine profiles at the time of administration. I mean, who knows? But I think it's a randomized trial, and I think I would expect to see a mad rush for treatment appointments early in the morning given this, and at least I want my patients to come in first thing in the morning. It'll be interesting to see. Dr. Nate Pennell: It's important to point out that in this study, everyone got chemo and immunotherapy. And, at least in our cancer center, most patients who are getting platinum-doublet chemotherapy and immunotherapy actually do get treated earlier in the day already, just because of the length of the infusion appointment that's needed. So it really is oftentimes people getting single-agent immunotherapy who are often getting the later, shorter visits. But if you have a choice, I think it would be very reasonable to have people treated earlier in the day. And I do think most of the impressions that I got from people about this is that they would like to see it reproduced but certainly well worth further investigation. And I personally would like to see more investigation into what the rationale would be for this because I still can't quite figure out, yes, if you got it at, say, you know, 5 PM, that's later in the day and I can understand that maybe your immune system is somewhat less receptive at that point than it would be in the morning. But because these checkpoint inhibitors have such long half-lives, it's still in your system the next morning when your immune system is supposedly more receptive. So I don't quite understand why that would be the case. Well, let's move on to the next study. I would like to hear your thoughts on Abstract 8515, “Plasma-Guided, Adaptive First-Line Chemoimmunotherapy for Non-Small Cell Lung Cancer.” Dr. Vamsi Velcheti: Yeah, this was another abstract that seems to be really interesting in my opinion. I think there's kind of a lot of emphasis lately on ctDNA and MRD-based assays to monitor disease. In the lung cancer space, we haven't had a lot of clinical trials looking at this prospectively, and this was one of those pilot studies where they looked at circulating free DNA (cfDNA)-based response-adaptive strategy for frontline patients who are PD-L1 positive. So, patients started with pembrolizumab monotherapy, and based on plasma molecular response after 2 cycles, those patients without response received early treatment intensification with a platinum doublet. So the approach essentially was to reduce the chemotherapy exposure in patients who respond to immunotherapy. And only about 17.5% of the patients on the trial received chemotherapy based on lack of molecular response. So, in this trial, what they found was patients with the cfDNA response had a markedly improved PFS of 16.4 months versus 4.8 months. So essentially, like, this is a really nice study to set a foundation on which we have to do larger studies to incorporate molecular markers trying to look at cfDNA response to inform treatment strategy, either escalation or de-escalation strategies. So, I thought it was a very interesting study. Dr. Nate Pennell: Yeah. I mean, we always have this question for patients, “Should they get immunotherapy alone or combined with chemo?” and I think this certainly is intriguing, suggesting that there may be ways you can monitor people and perhaps rescue those that aren't going to respond to single agent. I'd like to see a randomized trial against, you know, this strategy, perhaps against everyone getting, say, chemoimmunotherapy or make sure that you're not potentially harming people by doing this strategy. But I agree, it's time to move beyond just observing that cell-free DNA is prognostic and important and start using it to actually guide treatment. Dr. Vamsi Velcheti: Yeah, and I would just caution though, like, you know, I think we need more data, but, however, it's certainly a very interesting piece of data to kind of help inform future trials. So, there was another abstract that caught my attention, and I think this would be a very interesting abstract in the EGFR space. Abstract 8506, "Patritumab Deruxtecan (HER3-DXd) in Resistant EGFR-Mutant Advanced Non-Small Cell Lung Cancer Patients After Third-Generation EGFR TKI," it's the HERTHENA-Lung02 study. What do you think about the results of this study? Dr. Nate Pennell: Yeah, this was, I would say, very widely anticipated and ultimately a little disappointing, despite being a positive trial. So, these are patients with EGFR-mutant non-small cell lung cancer who have progressed after a third-generation EGFR TKI like osimertinib. This is really an area of major unmet need. We do have drugs like amivantamab in this space, but still definitely an area where essentially patients move from having a highly effective oral therapy to being in the realm of chemotherapy as their best option. So, this HER3 antibody-drug conjugate, patritumab deruxtecan, had some good single-arm data for this. And we're sort of hoping this would become an available option for patients. This trial was designed against platinum-doublet chemotherapy in this setting and with a primary endpoint of progression-free survival. And it actually was positive for improved progression-free survival compared to chemo with a hazard ratio of 0.77. But when you look at the medians, you can see that the median PFS was only 5.8 versus 5.4 months. It was really a modest difference between the two arms. And on the interim analysis, it appeared that there will not be a difference in overall survival between the two arms. In fact, the hazard ratio at the interim analysis was 0.98 for the two arms. So based on this, unfortunately, the company that developed the HER3-DXd has withdrawn their application to the FDA for approval of the drug, anticipating that they probably wouldn't get past approval without that overall survival endpoint. So, unfortunately, probably not, at least for the near future, going to be a new option for these patients. Dr. Vamsi Velcheti: Yeah, I think this is a space that's clearly an unmet need, and this was a big disappointment, I should say. I think all of us were going into the meeting anticipating some change in the standard of care here. Dr. Nate Pennell: Yeah, I agree. It was something that I was telling patients, honestly, that I was expecting this to be coming, and so now, definitely a bit of a disappointment. But it happens and, hopefully, it will still find perhaps a role or other drugs with a similar target. Certainly an active area. Well, let's leave the EGFR-mutant space and move into small cell. There were a couple of very impactful studies. And one of them was Abstract 8006, “Lurbinectedin Plus Atezolizumab as First-Line Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer, Primary Results from the Phase III IMforte Trial.” So, what was your impression of this? Dr. Vamsi Velcheti: Yeah, I think this is definitely an interesting study, and small cell, I remember those days when we had barely any studies of small cell at ASCO, and now we have a lot of exciting developments in the small cell space. It's really good to see. The IMforte trial is essentially like a maintenance lurbinectedin trial with atezolizumab maintenance. And the study was a positive trial. The primary endpoint was a PFS, and the study showed improvement in both PFS and OS with the addition of lurbinectedin to atezolizumab maintenance. And definitely, it's a positive trial, met its primary endpoint, but I always am a little skeptical of adding maintenance cytotoxic therapies here in this setting. In my practice, and I'd like to hear your opinion, Nate, most patients with small cell after 4 cycles of a platinum doublet, they're kind of really beaten up. Adding more cytotoxic therapy in the maintenance space is going to be tough, I think, for a lot of patients. But also, most importantly, I think this rapidly evolving landscape for patients with small cell lung cancer with multiple new, exciting agents, actually like some FDA-approved like tarlatamab, also like a lot of these emerging therapeutics like I-DXd and other ADCs in this space. You kind of wonder, is it really optimal strategy to bring on like another cytotoxic agent right after induction chemotherapy, or do you kind of delay that? Or maybe have like a different strategy in terms of maintenance. I know that the tarlatamab maintenance trial is probably going to read out at some point too. I think it's a little challenging. The hazard ratio is also 0.73. As I said, it's a positive trial, but it's just incremental benefit of adding lurbi. And also on the trial, we need to also pay attention to the post-progression second-line treatments, number of patients who received tarlatamab or any other investigational agents.  So I think it's a lot of questions still. I'm not quite sure I'd be able to embrace this completely. I think a vast majority of my patients might not be eligible anyway for cytotoxic chemotherapy maintenance right away, but yeah, it's tough. Dr. Nate Pennell: Yeah. I would call this a single and not a home run. It definitely is real. It was a real overall survival benefit. Certainly not surprising that a maintenance therapy would improve progression-free survival. We've known that for a long time in small cell, but first to really show an overall survival benefit. But I completely agree with you. I mean, many people are not going to want to continue further cytotoxics after 4 cycles of platinum-doublet chemo. So I would say, for those that are young and healthy and fly through chemo without a lot of toxicity, I think certainly something worth mentioning. The problem with small cell, of course, is that so many people get sick so quickly while on that observation period after first-line chemo that they don't make it to second-line treatment. And so, giving everyone maintenance therapy essentially ensures everyone gets that second-line treatment. But they also lose that potentially precious few months where they feel good and normal and are able to be off of treatment. So, I would say this is something where we're really going to have to kind of sit and have that shared decision-making visit with patients and decide what's meaningful to them. Dr. Vamsi Velcheti: Yeah, I agree. The next abstract that was a Late-Breaking Abstract, 8000, “Overall Survival of Neoadjuvant Nivolumab Plus Chemotherapy in Patients With Resectable Non-Small Cell Lung Cancer in CheckMate-816.” This was a highly anticipated read-out of the OS data from 816. What did you make of this abstract? Dr. Nate Pennell: Yeah, I thought this was great. Of course, CheckMate-816 changed practice a number of years ago when it first reported out. So, this was the first of the neoadjuvant or perioperative chemoimmunotherapy studies in resectable non-small cell lung cancer. So, just to review, this was a phase 3 study for patients with what we would now consider stage II or stage IIIA resectable non-small cell lung cancer. And they received three cycles of either chemotherapy or chemotherapy plus nivolumab, and that was it. That was the whole treatment. No adjuvant treatment was given afterwards. They went to resection. And patients who received the chemoimmunotherapy had a much higher pathologic complete response rate and a much better event-free survival. And based on this, this regimen was approved and, I think, at least in the United States, widely adopted.  Now, since the first presentation of CheckMate 816, there have been a number of perioperative studies that have included an adjuvant component of immunotherapy – KEYNOTE-671, the AEGEAN study – and these also have shown improved outcomes. The KEYNOTE study with pembrolizumab also with an overall survival benefit. And I think people forgot a little bit about CheckMate-816. So, this was the 5-year overall survival final analysis. And it did show a statistically and, I think, clinically meaningful difference in overall survival with the 3 cycles of neoadjuvant chemo-nivo compared to chemo with a hazard ratio of 0.72. The 5-year overall survival of 65% in the chemo-IO group versus 55% with the chemo alone. So a meaningful improvement. And interestingly, that hazard ratio of 0.72 is very similar to what was seen in the peri-operative pembro study that included the adjuvant component. So, very much still relevant for people who think that perhaps the value of those neoadjuvant treatments might be really where most of the impact comes from this type of approach. They also gave us an update on those with pathologic complete response, showing really astronomically good outcomes. If you have a pathologic complete response, which was more than a quarter of patients, the long-term survival was just phenomenal. I mean, 95% alive at 5 years if they were in that group and suggesting that in those patients at least, the adjuvant treatment may not be all that important.  So, I think this was an exciting update and still leaves very much the open question about the importance of continuing immunotherapy after surgery after the neoadjuvant component. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think the million-dollar question is: “Is there like a population of patients who don't have complete response but like maybe close to complete response?” So, would you like still consider stopping adjuvant IO? I probably would not be comfortable, but I think sometimes, you know, we all have patients who are like very apprehensive of continuing treatments. So, I think that we really need more studies, especially for those patients who don't achieve a complete CR. I think trying to find strategies for like de-escalation based on MRD or other risk factors. But we need more trials in that space to inform not just de-escalation, but there are some patients who don't respond at all to a neoadjuvant IO. So, there may be an opportunity for escalating adjuvant therapies. So, it is an interesting space to watch out for. Dr. Nate Pennell: No, absolutely. Moving to KRAS-mutant space, so our very common situation in patients with non-small cell lung cancer, we had the results of Abstract 8500, “First-Line Adagrasib With Pembrolizumab in Patients With Advanced or Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer” from the phase 2 portion of the KRYSTAL-7 study. Why was this an interesting and important study? Dr. Vamsi Velcheti: First of all, there were attempts to kind of combine KRASG12C inhibitors in the past with immune checkpoint inhibitors, notably sotorasib with pembrolizumab. Unfortunately, those trials have led to like a lot of toxicity, with increased especially liver toxicity, which was a major issue. This is a phase 2 study of adagrasib in combination with pembrolizumab, and this is a study in the frontline setting in patients with the G12C-mutant metastatic non-small cell lung cancer. And across all the PD-L1 groups, the ORR was 44%, and the median PFS was 11 months, comparable to the previous data that we have seen with adagrasib in this setting. So it's not like a major improvement in clinical efficacy. However, I think the toxicity profile that we were seeing was slightly better than the previous trials in combination with sotorasib, but you still have a fair amount of transaminitis even in the study. At this point, this is not ready for clinical primetime. I don't think we should be using sotorasib or adagrasib in the frontline or even in the second line in combination with checkpoint inhibitors. Combining these drugs with checkpoint inhibitors in the clinical practice might lead to adverse outcomes. So, we need to wait for more data like newer-generation G12C inhibitors which are also being studied in combination, so we'll have to kind of wait for more data to emerge in this space. Dr. Nate Pennell: I agree, this is not immediately practice changing. This is really an attempt to try to combine targeted treatment with immune checkpoint inhibitor. And I agree with you that, you know, it does appear to be perhaps a little bit better tolerated than some of the prior combinations that have tried in this space. The outcomes overall were not that impressive, although in the PD-L1 greater than 50%, it did have a better response rate perhaps than you would expect with either drug alone. And I do think that the company is focusing on that population for a future randomized trial, which certainly would inform this question better. But in the meantime, I agree with you, there's a lot of newer drugs that are coming along that potentially may be more active and better tolerated. And so, I'd say for now, interesting but we'll wait and see. Dr. Vamsi Velcheti: Yeah, so now moving back again to small cell. So, there was a Late-Breaking Abstract, 8008. This is a study of tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer. They presented the primary analysis of the phase III DeLLphi-304 study. What do you think about this? Dr. Nate Pennell: Yeah, I thought this was really exciting. This was, I would say, perhaps the most important lung study that was presented. Tarlatamab is, of course, the anti-DLL3 bispecific T-cell engager compound, which is already FDA approved based on a prior single-arm phase II study, which showed a very nice response rate as a single agent in previously treated small cell lung cancer and relatively manageable side effects, although somewhat unique to solid tumor docs in the use of these bispecific drugs in things like cytokine release syndrome and ICANS, the neurologic toxicities. So, this trial was important because tarlatamab was approved, but there were also other chemotherapy drugs approved in the previously treated space. And so, this was a head-to-head second-line competition comparison between tarlatamab and either topotecan, lurbinectedin, or amrubicin in previously treated small cell patients with a primary endpoint of overall survival. So, a very well-designed trial. And it did show, I think, a very impressive improvement in overall survival with a median overall survival in the tarlatamab group of 13.6 months compared to 8.3 months with chemotherapy, hazard ratio of 0.6. And progression-free survival was also longer at 4.2 months versus 3.2 months, hazard ratio of 0.72. In addition to showing improvements in cancer-related symptoms that were improved in tarlatamab compared to chemotherapy, there was actually also significantly lower rates of serious treatment-related adverse events with tarlatamab compared to chemotherapy. So, you do still see the cytokine release syndrome, which is seen in most people but is manageable because these patients are admitted to the hospital for the first two cycles, as well as a significant number of patients with neurologic side effects, the so-called ICANS, which also can be treated with steroids. And so, I think based upon the very significant improvement in outcomes, I would expect that this should become our kind of standard second-line treatment since it seems to be much better than chemo. However, tarlatamab is definitely a new drug that a lot of places are not used to using, and I think a lot of cancer centers, especially ones that aren't tied to a hospital, may have questions about how to deal with the CRS. So, I'm curious your thoughts on that. Dr. Vamsi Velcheti: Yeah, thank you, Nate. And I completely agree. I think the data looked really promising, and I've already been using tarlatamab in the second-line space. The durability of response and overall, having used tarlatamab quite a bit - like, I participated in some of the early trials and also used it as standard of care - tarlatamab has unique challenges in terms of like need for hospitalization for monitoring for the first few treatments and make sure, you know, we monitor those patients for CRS and ICANS. But once you get past that initial administration and monitoring of CRS, these patients have a much better quality of life, they're off chemotherapy, and I think it's really about the logistics of actually administering tarlatamab and coordination with the hospital and administration in the outpatient setting. It's definitely challenging, but I think it definitely can be done and should be done given what we are seeing in terms of clinical efficacy here. Dr. Nate Pennell: I agree. I think hospital systems now are just going to have to find a way to be able to get this on formulary and use it because it clearly seems to be more effective and generally better tolerated by patients. So, should move forward, I think. Finally, there's an abstract I wanted to ask you about, Abstract 8001, which is the “Neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in resectable epidermal growth factor receptor-mutated non-small cell lung cancer: The NeoADAURA Study”. And this is one that I think was also fairly highly anticipated. So, what are your thoughts? Dr. Vamsi Velcheti: You know, I wasn't probably surprised with the results, and I believe we were all expecting a positive trial, and we certainly were handed a positive trial here. It's a phase III trial of osimertinib and chemotherapy or osimertinib in the neoadjuvant space followed by surgery, followed by osimertinib. It's a global phase 3 trial and very well conducted, and patients with stage II to stage IIIB were enrolled in the study. And in the trial, patients who had a neoadjuvant osimertinib with or without chemotherapy showed a significant improvement in major pathologic response rates over chemotherapy alone. And the EFS was also positive for osimertinib and chemotherapy, osimertinib monotherapy as well compared to chemotherapy alone. So overall, the study met its primary endpoint, and I think it sheds light on how we manage our patients with early-stage lung cancer. I think osimertinib, we know that osimertinib is already FDA approved in the adjuvant space, but what we didn't really know is how was osimertinib going to work in the neoadjuvant space. And there are always situations, especially for stage III patients, where we are on the fence about, are these patients already close to being metastatic? They have, like, almost all these patients have micrometastatic disease, even if they have stage III. As we saw in the LAURA data, when you look at the control arm, it was like a very short PFS. Chemoradiation does nothing for those patients, and I think these patients have systemic mets, either gross or micrometastatic disease at onset. So, it's really important to incorporate osimertinib early in the treatment course. And I think, especially for the locally advanced patients, I think it's even more important to kind of incorporate osimertinib in the neoadjuvant space and get effective local control with surgery and treat them with adjuvant. I'm curious to hear your thoughts, Nate. Dr. Nate Pennell: I am a believer and have long been a believer in targeted adjuvant treatments, and, you know, it has always bothered me somewhat that we're using our far and away most effective systemic therapy; we wait until after they go through all their pre-op treatments, they go through surgery, then they go through chemotherapy, and then finally months later, they get their osimertinib, and it still clearly improves survival in the adjuvant setting. Why not just start the osimertinib as soon as you know that the patient has EGFR-mutant non-small cell lung cancer, and then you can move on to surgery and adjuvant treatment afterwards? And I think what was remarkable about this study is that all of these patients almost - 90% in each arm - went to surgery. So, you weren't harming them with the neoadjuvant treatment. And clearly better major pathologic response, nodal downstaging, event-free survival was better. But I don't know that this trial is ever going to show an overall survival difference between neoadjuvant versus just surgery and adjuvant treatment, given how effective the drug is in the adjuvant setting. Nonetheless, I think the data is compelling enough to consider this, certainly for our N2-positive, stage IIIA patients or a IIIB who might be otherwise surgical candidates. I think based on this, I would certainly consider that. Dr. Vamsi Velcheti: Yeah, and especially for EGFR, like even for stage IIIB patients, in the light of the LAURA study, those patients who do not do too well with chemoradiation. So you're kind of delaying effective systemic therapy, as you said, waiting for the chemoradiation to finish. So I think probably time to revisit how we kind of manage these locally advanced EGFR patients. Dr. Nate Pennell: Yep, I agree. Dr. Vamsi Velcheti: Nate, thank you so much for sharing your fantastic insights today on the ASCO Daily News Podcast. It's been an exciting ASCO again. You know, we've seen a lot of positive trials impacting our care of non-small cell lung cancer and small cell lung cancer patients. Dr. Nate Pennell: Thanks for inviting me, Vamsi. Always a pleasure to discuss these with you. Dr. Vamsi Velcheti: And thanks to our listeners for your time today. You will find links to all of the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:    Dr. Vamsi Velcheti   @VamsiVelcheti    Dr. Nathan Pennell   @n8pennell   Follow ASCO on social media:     @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn   ASCO on BlueSky   Disclosures:   Dr. Vamsi Velcheti:   Honoraria: ITeos Therapeutics   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus   Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Nathan Pennell:     Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron    Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

Del and Jefferey dive into the troubling numbers behind Merck's new RSV shot for infants, recently greenlit by the FDA. Trial data revealed higher rates of deaths and severe respiratory illness in vaccinated babies, yet the FDA overlooked this concerning trial data.Become a supporter of this podcast: https://www.spreaker.com/podcast/the-highwire-with-del-bigtree--3620606/support.

Dr. Shaalan Beg and Dr. Kristen Ciombor discuss practice-changing studies in GI cancers and other novel treatment approaches that were presented at the 2025 ASCO Annual Meeting. Transcript Dr. Shaalan Beg: Hello, I'm Dr. Shaalan Beg, welcoming you to the ASCO Daily News Podcast. I'm a medical oncologist and an adjunct associate professor at UT Southwestern Medical Center in Dallas, Texas. There were some remarkable advances in gastrointestinal cancers that were presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Kristen Ciombor to discuss some exciting GI data. Dr. Ciombor is the Ingram Associate Professor of Cancer Research and a co-leader of Translational Research and the Interventional Oncology Research Program at the Vanderbilt Ingram Cancer Center. Our full disclosures are available in the transcript of this episode. Dr. Ciombor, it's great to have you on the podcast today. Dr. Kristen Ciombor: Thanks, Dr Beg. It's great to be here. Dr. Shaalan Beg: Alright, let's kick it off. Big year for GI cancers. We'll start off with LBA1. This was the ATOMIC study sponsored by NCI and the National Clinical Trials Network (NCTN) and the Alliance group. This is a randomized study of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for stage III mismatch repair deficient colorectal cancer. Dr. Kristen Ciombor: I think this study was really definitely practice-changing, as you can tell because it was a Plenary. But I do have some concerns in terms of how we're actually going to implement this and whether this is the final answer in this disease subtype. So, as you said, the patients were enrolled with stage III resected mismatch repair deficient colon cancer, and then they were randomized to either modified FOLFOX6 with or without atezolizumab. And that's where it starts to become interesting because not many of us give FOLFOX for 6 months like was done in this study. Obviously, the study was done over many years, so that was part of that answer, but also the patients received atezolizumab for a total of 12 months. So the question, I think, that comes from this abstract is, is this practical and is this the final answer? I do think that this is practice-changing, and I will be talking to my patients with resected mismatch repair deficient colon cancer about FOLFOX plus atezolizumab. I think the big question is, do these patients need chemotherapy? And can we do a neoadjuvant approach instead? And that's where we don't have all the answers yet. Dr. Shaalan Beg: Yeah, but it has been great to see immunotherapy make its way into the adjuvant space after having made such a big impact in the metastatic space, but still some unanswered questions in terms of the need for chemotherapy and then the duration of therapy, which I guess we'll have to stay tuned in for the next couple of years to to get a lot of those questions answered. Dr. Kristen Ciombor: Yeah, but a big congratulations to the study team, to the NCTN, the NCI. I mean, this is really a great example of federally funded research that needs to continue. So, great job by the study team. The DFS 10% difference is really very large and certainly a practice-changing study. Dr. Shaalan Beg: Yeah, and and sticking with colon cancer, and and this another federally funded study, but this time funded by a Canadian cancer clinical trials group was LBA3510. This is the CHALLENGE study. It's a randomized phase 3 trial of the impact of a structured exercise program on disease-free survival for stage III or high-risk stage II colon cancer. This study got a lot of buzz, a lot of mainstream press coverage, and a lot of discussions on what that means for us for the patients who we're going to be seeing next week in our clinic. What was your takeaway? Dr. Kristen Ciombor: Yeah, this is a really interesting study, and I was so glad to see it presented because this partially answers one of the questions that patients always have for us in clinic, right? You know, once they've completed their standard chemotherapy and surgery, what else can they do to help prevent recurrence? And so we've always known and sort of extrapolated that healthy lifestyle habits are good, but now we have data, particularly in these patients. Most of them were stage III colon cancer patients, those had high-risk stage II cancer. And basically, the goal was to increase their physical activity by at least 10 MET hours per week. So, my big question, of course, as I came into this presentation was, “Okay, what does that mean exactly? How does that translate to real life?” And really what the author presented and explained was that basically most patients could hit their target by adding a 45- to 60-minute brisk walk 3 to 4 times a week. So I think this is very approachable.  Now, in the confines of the study, this was a structured exercise program, so it wasn't just patients doing this on their own. But I do think kind of extrapolating from that, that this is very achievable for most patients. And not only did this prevent recurrence of their prior cancer, but actually the rate of new primary cancer diagnoses, was less, which is really interesting, especially in the breast and prostate cancer. So this was a really interesting, and I think practice-changing study as well, especially given that this is something that most patients can do. Dr. Shaalan Beg: Yeah, and there was a lot of discussion in the hallways after the presentation in terms of how this really changes our existing practice because most folks already recommend exercise as a way for improving outcomes in cancer patients. So we've already been doing that. Now we have some data on how much it can impact the benefit. But there was some discussion about what the actual degree of impact was. There was a drop-off rate in terms of how long folks were able to stick with this exercise regimen. But you've seen this in clinic when someone have their surgery, they have their chemotherapy, they've been so intimately involved with the oncology world, with the oncology practice, and they somehow feel that they're being let loose into this mean, angry world without any guidance and they're looking for something to do. “What more can I do in terms of my lifestyle?” And then here we have very solid data, as solid as can be for an intervention like exercise, showing that there is an impact and you can give a prescription for exercise when someone wraps up their chemotherapy for colon cancer, thanks to the study. Dr. Kristen Ciombor: Yeah. It was a great study. Dr. Shaalan Beg: Moving to gastroesophageal cancer, another late-breaking abstract. This is LBA5. The MATTERHORN trial was a phase 3 trial of durvalumab plus FLOT for resectable GE junction and gastric cancer. And again, another area where immunotherapy has made an impact, and here we're seeing it move closer for earlier-stage disease. What was your take-home for the MATTERHORN trial? Dr. Kristen Ciombor: Yeah, so this study looked at neoadjuvant perioperative durvalumab plus our current standard chemotherapy of FLOT versus placebo plus FLOT. And this was a large study, almost 1,000 patients were randomized. And the primary endpoint was event-free survival, and it was definitely met in favor of the D + FLOT arm, as Dr. Klempner discussed after Dr Janjigian's presentation. I do think there are still some unanswered questions here. Overall survival is not yet mature, so we do have to wait and see how that shakes out. But it's very interesting and kind of is reflective of what, as you said, we're looking at earlier and earlier lines of therapy, particularly with immunotherapy, in these GI cancer spaces. So it makes a lot of sense to test this and and to look at this. So the toxicity was pretty similar to what we would expect. Primary endpoint was met, but again, we'll have to wait and see what the survival data looks like. Dr. Shaalan Beg: Yeah, and in oncology, we know, especially for treatment that does add additional cost, it does add additional potential toxicity that we want to see that overall survival nudged. I did see some polls on social media asking folks whether their practices changed from this, and I think the results were favoring adding durvalumab for this group of patients but understanding that there are caveats to the addition of treatments and the eventual FDA approval in that indication as well. Dr. Kristen Ciombor: Exactly. I completely agree with that. Dr. Shaalan Beg: All right. How about we stick with gastroesophageal cancer? LBA4002 was trastuzumab deruxtecan versus ramucirumab plus paclitaxel for second-line treatment in HER2-positive unresectable or metastatic gastric cancer or GE junction cancer. This was the DESTINY-Gastric04 study. And again, antibody-drug conjugates making a big impact across different diseases. And here we have more data in the HER2-positive gastric cancer space. Your thoughts on this study? Dr. Kristen Ciombor: Yeah, so this is a really important space in gastroesophageal cancer because the HER2 positivity rate is fairly high as compared to some of our other tumor types. So, I do think one of the important things was that patients did have biopsy confirmation of HER2 status, which was very important, and then they were randomized to either T-DXd versus the kind of second-line standard of ramucirumab-paclitaxel. So this was a great practical study and really answers a question that we had for a while in terms of does anti-HER2 therapy in the second-line really impact and improve survival. So we did see a statistically significant improvement favoring T-DXd. I do think it's always important to look at toxicity, though, too. And there was about almost 14% rate of interstitial lung disease, which of course is the most feared toxicity from some of these antibody-drug conjugates, especially T-DXd. So I do think it's important to keep that in mind, but this is definitely a great addition to the armamentarium for these HER2-positive patients. Dr. Shaalan Beg: And pancreas cancer was on the stage after a very long time with a positive clinical trial. This is Abstract 4006. These were preliminary results from a phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel alone for previously untreated metastatic pancreas cancer. This is a frontline clinical trial of gemcitabine/nab-paclitaxel plus/minus the study drug. There were other cohorts in this study as well, but they reported the results of their part 3B arm. And great to see some activity in the pancreas space. And your thoughts? Dr. Kristen Ciombor: Yeah, we definitely need better treatments in pancreas cancer. This was a very welcome presentation to see. The elraglusib is an inhibitor of GSK-3beta, and it's thought that that mediates drug resistance and EMT. And so this is, I think, a perfect setting to test this drug. So patients basically were randomized. Patients with metastatic pancreas cancer were randomized 2: 1 to gemcitabine/nab-paclitaxel plus or minus this elraglusib. So, what we saw was that overall survival was better with the addition of this new drug. And overall, not only the 1-year overall survival, but also median overall survival.  The thing that was interesting, though, was that we saw that the overall survival rates were 9.3 months with the combination versus 7.2 months with just gemcitabine/nab-paclitaxel. And that's a little bit lower than we've seen in other studies. So, not sure what was going on there. Was it the patients that were a bit sicker? Was it a patient selection, you know, thing? I'm not really sure how to explain that so much. Also, the toxicity profile was much higher in terms of visual impairment, with over 60% of patients being treated with the combination versus 9% with gemcitabine/nab-paclitaxel. So these were mild, grade 1 and 2, but still something to be cautious about. Dr. Shaalan Beg: And especially with this being a phase 2 trial, making sure that in a larger study we're able to better evaluate the toxicity and see if the control arm in the larger confirmatory study performs differently will be really important before this compound makes it to the clinic in our space. But very exciting to see these kinds of results for pancreas adenocarcinoma. Dr. Kristen Ciombor: Yeah. Dr. Shaalan Beg: We've talked, it seems, a couple of times on this podcast about the BREAKWATER clinical trial. We did hear PFS and updated OS data, updated overall survival data on first-line encorafenib plus cetuximab plus modified FOLFOX6 for BRAF-mutated colorectal cancer. This was LBA3500. And eagerly anticipated results – we have all previously heard the progression-free survival results – but here we heard updated overall survival results, and very well-received study it seemed from the audience that time. So what are your takeaways on the updated results for BREAKWATER? Dr. Kristen Ciombor: In my opinion, this was one of the most practice-confirming studies. As you mentioned, we've already seen some of the preliminary data of BREAKWATER at prior meetings. But really what was particularly impactful for me was the median overall survival with the BREAKWATER regimen. So, again, patients received FOLFOX, encorafenib cetuximab in the first line if they had BRAF-mutated V600E-mutated colorectal cancer. And the median PFS was 12.8 months, which was actually really remarkable in this traditionally very aggressive, poor prognosis subtype of tumors. So, by seeing a median overall survival of 30.3 months was just incredible, in my opinion. Just a few years ago, that was considered the median overall survival for all comers for metastatic colorectal cancer. And we know the median overall survival was more in the less than 12 months range for BRAF. So this was incredibly impactful, and I think should be absolutely practice-changing for anyone who is eligible for this regimen.  I think again, where the practice meets the study is what's kind of important to think about too, how long did patients get FOLFOX, and certainly it adds toxicity to add a BRAF-targeted regimen on top of FOLFOX already. So, one of the other interesting things about the study, though, was that even though it didn't complete treatment, they actually did look at encorafenib/cetuximab alone and in the first line without chemotherapy. And those preliminary results actually looked okay, especially for patients who might not be able to tolerate chemotherapy, which we certainly see in practice. So, overall, definitely more data. And I agree that it's certainly practice-changing. Dr. Shaalan Beg: And it completely, as you mentioned, changes the outlook for a person who's diagnosed with BRAF-mutated metastatic colon cancer today versus even 7 or 8 years ago. Dr. Kristen Ciombor: And we're seeing this over and over in other subtypes too, but how you choose to treat the patient up front really matters. So really giving the right regimen up front is the key here. Dr. Shaalan Beg: And along the same lines, Abstract 3501 wanted to answer the question on whether people with MSI-high metastatic colorectal cancer need double checkpoint inhibitor therapy or is single therapy enough. So this [CheckMate-8HW] study compared nivo plus ipi with nivo alone, nivo monotherapy for MSI-high metastatic colorectal cancer. And we've known that both of these are fairly active regimens, but we also know the chance of immune-related adverse events is significantly higher with combination therapy. So this was a much-needed study for this group of patients. And what were your takeaways here? Dr. Kristen Ciombor: This, of course, has been really nivo-ipi in the first-line MSI-high metastatic colorectal cancer is now a standard of care. And not everybody is eligible for it, and there could be reasons, toxicity reasons, and other things too. But as we've been seeing for the last couple of years, immunotherapy clearly beats chemo in this space. And now looking at doublet versus single immunotherapy treatment in the first line, I think really nivo-ipi does beat out monotherapy. I will say, however, there is a caveat in that we still haven't seen the nivo-ipi versus nivo in the first line. So what has been presented thus far has been across all lines of therapy, and that does muddy the waters a little bit. So definitely looking forward and and we've asked this many times and based on the statistical plan and and what not, you know, we just haven't seen that data yet. But I do think it's becoming increasingly important to consider doublet immunotherapy for these patients as long as there are no contraindications. With the again, with the caveat that we have to have these toxicity discussions in the clinic with patients because many patients can tolerate it, you know, this regimen fairly well, but there can be very severe toxicities. So, I think an informed discussion should really be had with each patient before moving forward. Dr. Shaalan Beg: Yeah, informed decision, making them aware of the potential of real significant toxicities, immune-related toxicities with double therapy. But I am curious in your practice, how often do you see people choosing doublet therapy as frontline? Dr. Kristen Ciombor: So patients are really savvy, and a lot of times they've heard this data before or have come across it in patient advocacy groups and other things, and it's really nice to be able to have that conversation of the risk versus benefit. So I will say not all of my patients choose doublet, and many of them are still cured with immunotherapy monotherapy. So the big question there is, will we ever understand who actually needs the doublet versus who can still be cured or have very good long-term outcomes with just the single agent? And that has not been answered yet. Dr. Shaalan Beg: What a great point. So the last abstract I was hoping we could talk about is POD1UM-303 or the INTERAACT2 subgroup analysis and impact of delayed retifanlimab treatment for patients with squamous cell carcinoma of the anal canal. What were your thoughts here? Dr. Kristen Ciombor: This was a study, actually we saw at ESMO, we saw the primary data at ESMO last year, and this was an update with some exploratory analyses. But this was really an important study because once again, we're looking at immunotherapy in later lines of therapy. That's how we started looking at and investigating immunotherapy, and now we're moving it up and up in the treatment course. So this was a study of carboplatin/paclitaxel plus or minus retifanlimab. Actually it was retifanlimab versus placebo. And it was a positive study, as we heard last year. This actually led to FDA approval of this regimen last month, just before ASCO, and it has now been incorporated in the NCCN guidelines as the preferred first-line option.  So what I thought was important from the additional data presented at ASCO was looking at the different subgroups, it did not appear that patients with liver mets or not had different outcomes. So that was really good to see because sometimes in colon cancer we see that immunotherapy doesn't work as well when patients have liver mets. And interestingly, because we use immunotherapy in anal cancer without any biomarkers, unlike with colon cancer or some of the other tumor types, also the authors looked at PD-L1 status, and it did look like maybe patients did a little bit better if they had higher PD-L1 expression, but patients still could benefit even if they were PD-L1 negative. So that was important, I think, and we will continue to see further data come out from this study. I want to mention also that EA2176 just completed accrual, so that was carbo-taxol plus or minus nivolumab. And so we should be seeing that data sometime soon, which will hopefully also confirm the ongoing role for immunotherapy in the first-line setting for anal cancer. Dr. Shaalan Beg: That was a fantastic review. Thank you, Dr Ciombor. Thanks for sharing your valuable insights with us today on the ASCO Daily News Podcast. Dr. Kristen Ciombor: Thanks for having me here. Dr. Shaalan Beg: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. And if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe, wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:   Dr. Shaalan Beg  @ShaalanBeg  Dr. Kristen Ciombor @KristenCiombor Follow ASCO on social media:    @ASCO on Twitter   @ASCO on BlueSky  ASCO on Facebook    ASCO on LinkedIn    Disclosures:   Dr. Shaalan Beg:   Consulting or Advisory Role: Ipsen, Cancer Commons, Foundation Medicine, Science37, Nant Health, Lindus Health Speakers' Bureau: Sirtex Research Funding (Inst.): Delfi Diagnostics, Universal Diagnostics, Freenome Dr. Kristen Ciombor: Consulting or Advisory Role: Pfizer, Incyte, Exelixis, Bayer, ALX Oncology, Tempus, Agenus, Taiho Oncology, Merck, BeiGene Research Funding (Inst.): Pfizer, Boston Biomedical, MedImmune, Onyx, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Incyte, Amgen, Sanofi, Bristol-Myers Squibb, Array BioPharma, Incyte, Daiichi Sankyo, Nucana, Abbvie, Merck, Pfizer/Calthera, Genentech, Seagen, Syndax Travel, Accommodations, Expenses: Incyte, Tempus

Michael J. Gelb is a pioneer in the fields of creative thinking, innovative leadership and executive coaching. His clients include DuPont, Emerson, Genentech, KPMG, Merck, Microsoft, Nike and YPO. Michael trained as a teacher of the Alexander Technique and holds a fifth-degree black belt in the martial art of Aikido. Michael is the author of 18 books which have been translated into 25 languages and have sold more than one million copies. They include How to Think Like Leonardo Da Vinci, The Healing Organization and Walking Well: A New Approach for Comfort, Vitality and Inspiration in Every Step with Bruce Fertman.   Here he and Dawson discuss: Where we hold our traumas “Character armor” Why our old patterns are embedded, and change is hard. What can we do? Benefits of EFT, walking, qigong, and meditation  Expanding rather than contracting As well as trauma triggers, we can find glimmers that remind us of wellbeing Finding your glimmer.  A day in the life of Michael Gelb: his personal practices for wellbeing How is body awareness linked to spirituality?   To learn more about Michael Gelb: https://michaelgelb.com/   Find host Dr. Dawson Church at: http://dawsongift.com/   To order Dawson's newest book, Spiritual Intelligence:  https://www.amazon.com/Spiritual-Intelligence-Activating-Circuits-Awakened/dp/160415294X/   #mindtomatter #blissbrain #spiritualintelligence #eft #meditation #highenergyhealth #sq #creativity #innovation #leadership

Join us on the latest episode, hosted by Jared S. Taylor!Our Guest: Bill Taranto, President at Merck Global Health Innovation Fund.What you'll get out of this episode:Bill Taranto's Journey: From Johnson & Johnson to leading Merck's $600M GHI Fund focused on digital health and technology.Four Core Investment Areas: Drug discovery, clinical development, supply chain, and patient access/data.Portfolio Spotlights: Companies like Npower, Unnatural Products, Aerosafe Global, Cure AI, and Prognos are driving impactful innovation.Strategic Value of CVCs: Beyond capital, CVCs offer startups technical expertise, commercial agreements, and long-term support.Navigating Market Challenges: Insights on VC pullback, consolidation trends, and advice for startups on sustainable growth.To learn more about Merck:Website https://www.merck.com/ Linkedin https://www.linkedin.com/company/merck/Our sponsors for this episode are:Sage Growth Partners https://www.sage-growth.com/Quantum Health https://www.quantum-health.com/Show and Host's Socials:Slice of HealthcareLinkedIn: https://www.linkedin.com/company/sliceofhealthcare/Jared S TaylorLinkedIn: https://www.linkedin.com/in/jaredstaylor/WHAT IS SLICE OF HEALTHCARE?The go-to site for digital health executive/provider interviews, technology updates, and industry news. Listed to in 65+ countries.

US equity markets fell as the Israel-Iran conflict continued to dominate investor sentiment and drive volatility and a fresh spike in oil prices - Dow lost -299-points or -0.70%. Merck & Co Inc (down -3.31%) and Nike Inc (-3.07%) both fell over >3%. Amazon.com Inc (down -0.59%) said its Prime Day discount event for Prime members next month will extend to four days (8 July-11 July). 

Audio roundup of selected biopharma industry content from Scrip over the business week ended 13 June 2025. In this episode: breaking down big pharma's executive pay; US vaccine panel upheaval; Merck's RSV approval; MFN and Japan; and the future of Pfizer and Arvinas's partnership. https://insights.citeline.com/scrip/podcasts/scrips-five-must-know-things/quick-listen-scrips-five-must-know-things-BC44NPMNMNGMXP5X4STR4ZAFU4/ This episode was produced with the help of AI text-to-voice and voice emulation tools. Playlist: soundcloud.com/citelinesounds/sets/scrips-five-must-know-things

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Two new members of Kennedy's revamped CDC vaccine advisory committee, Martin Kulldorff and Robert Malone, have a history of being paid expert witnesses in vaccine cases against Merck. They are known for being vaccine skeptics and have questioned the use of mRNA technology in vaccines. Meanwhile, Moderna has received an expanded label for its mRNA RSV shot, but there are concerns about the new ACIP members' questioning of mRNA technology.In other news, Astrazeneca has made a $5.3 billion bet on AI with China's CSPC for chronic disease pills. ADC Therapeutics is cutting staff and closing a research facility, while Biontech has acquired vaccine rival Curevac. The AMA has called for a Senate probe into RFK Jr. after the removal of CDC vaccine advisors.Overall, the industry is facing challenges with layoffs and a tight job market.

In his weekly clinical update, Dr. Griffin with Vincent Racaniello in horror examine dismantling of public infrastructure for establishing vaccine guidelines, the creation of a autism taskforce by someone disciplined for practicing medicine without a license, the ongoing pertussis, bird flu and measles outbreaks, before Dr. Griffin reviews recent statistics on RSV, influenza and SARS-CoV-2 infections the Wasterwater Scan dashboard, the effective of oseltamivir vs supportive care when one is hospitalized with influenza infection, whether or not the NB.1.8.1 should be included in the fall 2025 vaccines, approval of another anti-RSV monoclonal antibody for treatment in infants, immunization recommendations for COVID-19 vaccines, where to find PEMGARDA, results from the phase 3 randomized clinical trial of pemivibart, provides information for Columbia University Irving Medical Center's long COVID treatment center, where to go for answers to your long COVID questions, how artery disease impacts SARS-CoV-2 infection outcomes, contacting your federal government representative to stop the assault on science and biomedical research and the recent public health programs that have been unfunded. Subscribe (free): Apple Podcasts, RSS, email Become a patron of TWiV! Links for this episode Vaccine Opponent Hired by RFK Jr. Scours Official Records for Link to Autism (Wall Street Journal) Correcting our record (Salon) You are FIRED! Kennedy removes all ACIP members, eyes replacement (CIDRAP) UPI Investigates: The vaccine conflict…..investigative reporting? (UPI) RFK Jr.: HHS Moves to Restore Public Trust in Vaccines…to avoid conflicts UGHHHH! (Wall Street Journal) GREAT Vaccine advisory panel (Great Barrington Declaration) National Vaccine Information Center (Wikipedia: National Vaccine Information Center) Nonprofit organization 501(c)  (Wikipedia) Kennedy Announces Eight New Members of C.D.C. Vaccine Advisory Panel (NY Times) Whooping cough deaths! (Kentucky. Gov) Kentucky announces two pertussis deaths in infants this year (CIDRAP) H5 bird flu: current situation (CDC: Avian Influenza) Stability of influenza viruses in the milk of cows and sheep (medRxiv) Wastewater for measles (WasterWater Scan) Measles cases and outbreaks (CDC Rubeola) Weekly measles and rubella monitoring (Government of Canada) Canada's Ontario province reports death of child from measles (Reuters) Measles outbreaks continue with risk of holidays causing surge (gov.UK) Measles (WHO) Measles vaccine recommendations from NYP (jpg) Get the FACTS about measles (NY State Department of Health) Measles (CDC Measles (Rubeola)) Measles vaccine (CDC Measles (Rubeola)) Presumptive evidence of measles immunity (CDC) Contraindications and precautions to measles vaccination (CDC) Measles (CDC Measles (Rubeola) Adverse events associated with childhood vaccines: evidence bearing on causality (NLM) Measles Vaccination: Know the Facts (ISDA: Infectious Diseases Society of America) Deaths following vaccination: what does the evidence show (Vaccine) Influenza: Waste water scan for 11 pathogens (WastewaterSCan) US respiratory virus activity (CDC Respiratory Illnesses) Weekly surveillance report: clift notes (CDC FluView) Respiratory virus activity levels (CDC Respiratory Illnesses) Weekly surveillance report: clift notes (CDC FluView) Oseltamivir Treatment vs Supportive Care for Seasonal Influenza Requiring Hospitalization (JAMA) FDA-CDC-DOD: 2025-2046 influenza vaccine composition (FDA) RSV: Waste water scan for 11 pathogens (WastewaterSCan) US respiratory virus activity (CDC Respiratory Illnesses) RSV-Network (CDC Respiratory Syncytial virus Infection) Approval for Merck's ENFLONSIA™ (clesrovimab-cfor) for Prevention of Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Disease in Infants Born During or Entering Their First RSV Season (Merck) Waste water scan for 11 pathogens (WastewaterSCan) COVID-19 deaths (CDC) COVID-19 national and regional trends (CDC) COVID-19 variant tracker (CDC) SARS-CoV-2 genomes galore (Nextstrain) Antigenic and Virological Characteristics of SARS-CoV-2 Variant BA.3.2, XFG, and NB.1.8.1 (biRxiV) COVID-19 vaccine for 6 months, 12 years (CDC: childhood vaccination) COVID-19 vaccine for65 years and older (CDC: Adult vaccination) Where to get pemgarda (Pemgarda) EUA for the pre-exposure prophylaxis of COVID-19 (INVIYD) Infusion center (Prime Fusions) CDC Quarantine guidelines (CDC) NIH COVID-19 treatment guidelines (NIH) Drug interaction checker (University of Liverpool) Infectious Disease Society guidelines for treatment and management (ID Society) Molnupiravir safety and efficacy (JMV) Convalescent plasma recommendation for immunocompromised (ID Society) What to do when sick with a respiratory virus (CDC) Managing healthcare staffing shortages (CDC) Steroids,dexamethasone at the right time (OFID) Anticoagulation guidelines (hematology.org) Daniel Griffin's evidence based medical practices for long COVID (OFID) Long COVID hotline (Columbia : Columbia University Irving Medical Center) The answers: Long COVID Long-term outcomes of patients with pre-existing coronary artery disease after SARS-CoV-2 infection (eBioMedicine) Reaching out to US house representative Trump Budget Eliminates Funding for Crucial Global Vaccination Programs(NY Times) Letters read on TWiV 1226 Dr. Griffin's COVID treatment summary (pdf) Timestamps by Jolene Ramsey. Thanks! Intro music is by Ronald Jenkees Send your questions for Dr. Griffin to daniel@microbe.tv Content in this podcast should not be construed as medical advice.

Dr. William Soliman is the founder and CEO of the Accreditation Council for Medical Affairs (ACMA). The ACMA is America's leader in life sciences accreditation, certification & training.  Soliman is a former pharmaceutical executive who worked in leadership roles at Merck, Abbvie, Gilead and more. He is considered a pharma industry futurist and has been featured on NewsNation, Fox News, Newsmax, Forbes, Al Jazeera, Yahoo Business TV, ABC News Radio & more. The ACMA established the first ever certification standards in the United States and stands as a benchmark of excellence for prior authorization professionals, reimbursement professionals, pharmaceutical sales professionals, medical science liaisons and medical affairs professionals.  Dr. Soliman received his PhD from Columbia University & his BA from New York University.

Welcome to this new episode of Beyond the Thesis with Papa PhD! In this episode, host David Mendes sits down with Morgan Foret, who brings a fresh perspective on navigating the journey from academia to industry. Morgan shares her personal story, beginning with her undergraduate studies in cell biology, an international research internship in Germany, and her PhD in pharmacology at McGill University, where she focused on Alzheimer's disease. Now working in regulatory affairs at Thermo Fisher, Morgan discusses the realities and misconceptions of moving into industry after a PhD. Together, David and Morgan unpack the challenges she faced and the transferable skills and career strategies that helped her smoothly transition out of academia and into regulatory affairs.   Morgan Foret's journey in science began at the University of Calgary, where she earned her undergraduate degree in cell biology. Driven by curiosity, Morgan spent a year on academic exchange at Lund University in Sweden, conducting undergraduate research that expanded her international perspective. Back in Calgary, she explored the world of nanoparticles and lung cells, gaining hands-on experience using an atomic force microscope, a time she remembers fondly for the engaging research and the thrill of discovery. After graduation, Morgan pursued an industry internship in Germany through the DAAD RISE Professional program, spending three months at Merck in Darmstadt. There, she crossed into the world of industrial research, getting a firsthand look at how scientific discoveries move from lab to industry. Throughout her journey, Morgan has combined academic excellence, international experience, and research initiative, shaping her as a promising and well-rounded scientist. What we covered in the interview: Embrace Hands-On Industry Experience Early: Programs like the DAAD RISE internship in Germany or organizing/attending industry networking events during your studies are game-changers, helping you understand how your research background can translate to industry roles and widen your global perspective. Leverage Transferable Skills, Not Just Your Title: Don't underestimate the power of skills honed during your academic journey—project management, communication, collaboration, and resilience. Learn to highlight these when applying for roles, even if your previous title doesn't match the new one exactly.  Stay Curious & Build Your “Organic” Network: Networking doesn't have to be intimidating or formal. Reach out to peers a year or two ahead of you, connect with alumni, or even organize your own events. Be guided by curiosity; those casual conversations can open doors and demystify the industry landscape. Whether you're considering a move to industry or just want to understand what really happens after the PhD, this episode is packed with practical advice, personal anecdotes, and inspiration. See the resources section below for Morgan Foret's links! This episode's resources: RAPS Quebec Local Networking Group| linkedin.com/showcase/raps-quebec-local-networking-group PCSN (Pharmaceutical Career Student Network, student group at McGill) | linkedin.com/company/pcsn-mcgill Women in Bio Montreal Chapter | linkedin.com/showcase/wib-greater-montreal Women Leaders in Pharma | linkedin.com/company/women-leaders-in-pharma Healthcare Business Women's Association | linkedin.com/showcase/hba-canada-region Thank you, Morgan Foret! If you enjoyed this conversation with Morgan, let her know by clicking the link below and leaving her a message on Linkedin: Send Morgan Foret a thank you message on Linkedin! Click here to share your key take-away from this interview with David! Leave a review on Podchaser ! Support the show !   You might also like the following episodes: Sarah McLusky – Research Adjacent Podcast Collab Colleen Kelley – Unlocking Science Literacy Before University Rayana Luna –Navigating Medical Affairs Careers Sylvie Lahaie – Navigating Stress and Anxiety in Graduate School

In this episode, we continue with a special series close to my heart: Decoding Destiny: Navigating Breast Cancer with Genetic Insight. I'm joined by Kathy Baker, patient advocate and founder of My Faulty Gene to explore the power of genetic testing—particularly cascade testing—and how it can help both you and your family take control of your breast cancer risk. Kathy shares her compelling personal story and how it inspired her to launch My Faulty Gene, a nonprofit organization that provides education, emotional support, and financial assistance for genetic testing. You'll learn all about the importance of cascade testing for families, how genetic knowledge can lead to proactive screenings and preventive health measures, and how advocacy is truly paving the way for more accessible care. Whether you're facing a BRCA-positive diagnosis, considering genetic testing, or looking for support navigating hereditary cancer risk, this is one conversation that you'll want to listen to - and share with your entire family.  Thank you to Merck and AstraZeneca for making this episode possible!

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Robert F. Kennedy Jr.'s removal of all members of the CDC's Advisory Committee on Immunization Practices has raised concerns about the upcoming meeting later this month. Analysts fear that the committee may become more sympathetic to anti-vaccine viewpoints. In other news, Merck has received FDA approval for an RSV antibody, Gilead has paused five HIV trials but Lenacapavir remains safe, and the FDA has reinstated a previously disbanded generic drug policy panel. Gilead has expressed faith in its HIV combo therapy and pledged to work with regulators to resolve the hold on its trials. In vitro cell research is focused on discovering interventions to slow aging and prevent age-related diseases.Kennedy's vaccine campaign is seen as breeding more distrust, while Metsera's weight loss injection has shown positive results. Merck is moving forward with an oral PCSK9 inhibitor. Thank you for tuning in to Pharma and Biotech daily for the latest updates in the pharmaceutical and biotechnology industries.

June 10, 2025 | This episode of The Chain features a panel discussion from May's PEGS Boston. Moderated by Peter Tessier, Albert M. Mattocks professor of Pharmaceutical Sciences and Chemical Engineering at the University of Michigan, the panelists include Sarel Fleishman, professor of Biomolecular Sciences at the Weizmann Institute of Science; Kadina Johnston, senior specialist of Discovery Biologics at Merck & Co.; Vincent Ling, chief business officer of Morphocell Technologies; Arvind Rajpal, SVP of Xaira; and Max Vasquez, chief computing officer of Adimab. Together they discuss benchmarking AI/ML methods compared to traditional approaches, development of human-relevant training data, identifying and addressing core challenges in de novo designs, and more. Links from this episode:  PEGS Boston Conference & Expo Engineering Bispecific Antibodies University of Michigan University of Michigan Chemical Engineering Weizmann Institute of Science Scala Biodesign Merck & Co., Inc. Morphocell Technologies Bill & Melinda Gates Foundation Xaira Adimab LLC 

Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in Pharma and Biotech world. Metsera's new long-acting amylin injection, met-233i, has shown promising weight loss results over eight months, leading to a rise in shares. Meanwhile, CDC vaccine advisors are either being pushed out or leaving their positions. Other top stories include Sirna's expansion beyond the liver, Keros returning $375 million to investors, and ACIP members receiving termination notices. In vitro cell research is focused on slowing aging and preventing age-related diseases. Updates on Merck's oral PCSK9 inhibitor, Sanofi and Regeneron's Dupixent effectiveness, and Avidity's muscular dystrophy drug are also highlighted.The expansion of RNA therapeutics is discussed, with multiple companies aiming to target small interfering RNA to various organs by 2030. Uniqure's regulatory progress in developing a gene therapy for Huntington's disease has sparked optimism, although past disappointments for patients are noted. Perspective Therapeutics presents new data on neuroendocrine tumor treatment at ASCO25. Concerns about RFK Jr.'s vaccine campaign and its potential to increase distrust in vaccines are raised in the editorial. Cancer news, cell and gene therapy updates, upcoming events, job listings, and a call for reader suggestions on coverage topics are also covered.

John Schloegel shares his market insights and favorite undervalued businesses, including Merck & Co. (MRK) and PepsiCo (PEP). He also discusses the potential for a pullback in the 60/40 portfolio and why he's not convinced it's dead yet. He emphasizes the importance of patience and long-term thinking, citing Warren Buffett's advice to only need one or two good investment opportunities every few years to be successful.======== Schwab Network ========Empowering every investor and trader, every market day. Subscribe to the Market Minute newsletter - https://schwabnetwork.com/subscribeDownload the iOS app - https://apps.apple.com/us/app/schwab-network/id1460719185Download the Amazon Fire Tv App - https://www.amazon.com/TD-Ameritrade-Network/dp/B07KRD76C7Watch on Sling - https://watch.sling.com/1/asset/191928615bd8d47686f94682aefaa007/watchWatch on Vizio - https://www.vizio.com/en/watchfreeplus-exploreWatch on DistroTV - https://www.distro.tv/live/schwab-network/Follow us on X – https://twitter.com/schwabnetworkFollow us on Facebook – https://www.facebook.com/schwabnetworkFollow us on LinkedIn - https://www.linkedin.com/company/schwab-network/ About Schwab Network - https://schwabnetwork.com/about

Dr. Nathan Pennell and Dr. Cheryl Czerlanis discuss challenges in lung cancer screening and potential solutions to increase screening rates, including the use of AI to enhance risk prediction and screening processes. Transcript Dr. Nate Pennell: Hello, and welcome to By the Book, a monthly podcast series for ASCO Education that features engaging discussions between editors and authors from the ASCO Educational Book. I'm Dr. Nate Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and vice chair of clinical research for the Taussig Cancer Center. I'm also the editor-in-chief for the ASCO Educational Book.  Lung cancer is one of the leading causes of cancer-related mortality worldwide, and most cases are diagnosed at advanced stages where curative treatment options are limited. On the opposite end, early-stage lung cancers are very curable. If only we could find more patients at that early stage, an approach that has revolutionized survival for other cancer types such as colorectal and breast cancer.  On today's episode, I'm delighted to be joined by Dr. Cheryl Czerlanis, a professor of medicine and thoracic medical oncologist at the University of Wisconsin Carbone Cancer Center, to discuss her article titled, "Broadening the Net: Overcoming Challenges and Embracing Novel Technologies in Lung Cancer Screening." The article was recently published in the ASCO Educational Book and featured in an Education Session at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Cheryl, it's great to have you on the podcast today. Thanks for being here. Dr. Cheryl Czerlanis: Thanks, Nate. It's great to be here with you. Dr. Nate Pennell: So, I'd like to just start by asking you a little bit about the importance of lung cancer screening and what evidence is there that lung cancer screening is beneficial. Dr. Cheryl Czerlanis: Thank you. Lung cancer screening is extremely important because we know that lung cancer survival is closely tied to stage at diagnosis. We have made significant progress in the treatment of lung cancer, especially over the past decade, with the introduction of immunotherapies and targeted therapies based on personalized evaluation of genomic alterations. But the reality is that outside of a lung screening program, most patients with lung cancer present with symptoms related to advanced cancer, where our ability to cure the disease is more limited.  While lung cancer screening has been studied for years, the National Lung Screening Trial, or the NLST, first reported in 2011 a significant reduction in lung cancer deaths through screening. Annual low-dose CT scans were performed in a high-risk population for lung cancer in comparison to chest X-ray. The study population was comprised of asymptomatic persons aged 55 to 74 with a 30-pack-year history of smoking who were either active smokers or had quit within 15 years. The low-dose CT screening was associated with a 20% relative risk reduction in lung cancer-related mortality. A similar magnitude of benefit was also reported in the NELSON trial, which was a large European randomized trial comparing low-dose CT with a control group receiving no screening. Dr. Nate Pennell: So, this led, of course, to approval from CMS (Centers for Medicare and Medicaid Services) for lung cancer screening in the Medicare population, probably about 10 years ago now, I think. And there are now two major trials showing an unequivocal reduction in lung cancer-related mortality and even evidence that it reduces overall mortality with lung cancer screening. But despite this, lung cancer screening rates are very low in the United States. So, first of all, what's going on? Why are we not seeing the kinds of screening rates that we see with mammography and colonoscopy? And what are the barriers to that here? Dr. Cheryl Czerlanis: That's a great question. Thank you, Nate. In the United States, recruitment for lung cancer screening programs has faced numerous challenges, including those related to socioeconomic, cultural, logistical, and even racial disparities. Our current lung cancer screening guidelines are somewhat imprecise and often fail to address differences that we know exist in sex, smoking history, socioeconomic status, and ethnicity. We also see underrepresentation in certain groups, including African Americans and other minorities, and special populations, including individuals with HIV. And even where lung cancer screening is readily available and we have evidence of its efficacy, uptake can be low due to both provider and patient factors. On the provider side, barriers include having insufficient time in a clinic visit for shared decision-making, fear of missed test results, lack of awareness about current guidelines, concerns about cost, potential harms, and evaluating both true and false-positive test results.  And then on the patient side, barriers include concerns about cost, fear of getting a cancer diagnosis, stigma associated with tobacco smoking, and misconceptions about the treatability of lung cancer. Dr. Nate Pennell: I think those last two are really what make lung cancer unique compared to, say, for example, breast cancer, where there really is a public acceptance of the value of mammography and that breast cancer is no one's fault and that it really is embraced as an active way you can take care of yourself by getting your breast cancer screening. Whereas in lung cancer, between the stigma of smoking and the concern that, you know, it's a death sentence, I think we really have some work to be made up, which we'll talk about in a minute about what we can do to help improve this.  Now, that's in the U.S. I think things are probably, I would imagine, even worse when we leave the U.S. and look outside, especially at low- and middle-income countries. Dr. Cheryl Czerlanis: Yes, globally, this issue is even more complex than it is in the United States. Widespread implementation of low-dose CT imaging for lung cancer screening is limited by manpower, infrastructure, and economic constraints. Many low- and middle-income countries even lack sufficient CT machines, trained personnel, and specialized facilities for accurate and timely screenings. Even in urban centers with advanced diagnostic facilities, the high screening and follow-up care costs can limit access. Rural populations face additional barriers, such as geographic inaccessibility of urban centers, transportation costs, language barriers, and mistrust of healthcare systems. In addition, healthcare systems in these regions often prioritize infectious diseases and maternal health, leaving limited room for investments in noncommunicable disease prevention like lung cancer screening. Policymakers often struggle to justify allocating resources to lung cancer screening when immediate healthcare needs remain unmet. Urban-rural disparities exacerbate these challenges, with rural regions frequently lacking the infrastructure and resources to sustain screening programs. Dr. Nate Pennell: Well, it's certainly an intimidating problem to try to reduce these disparities, especially between the U.S. and low- and middle-income countries. So, what are some of the potential solutions, both here in the U.S. and internationally, that we can do to try to increase the rates of lung cancer screening? Dr. Cheryl Czerlanis: The good news is that we can take steps to address these challenges, but a multifaceted approach is needed. Public awareness campaigns focused on the benefits of early detection and dispelling myths about lung cancer screening are essential to improving participation rates. Using risk-prediction models to identify high-risk individuals can increase the efficiency of lung cancer screening programs. Automated follow-up reminders and screening navigators can also ensure timely referrals and reduce delays in diagnosis and treatment. Reducing or subsidizing the cost of low-dose CT scans, especially in low- or middle-income countries, can improve accessibility. Deploying mobile CT scanners can expand access to rural and underserved areas.  On a global scale, integrating lung cancer screening with existing healthcare programs, such as TB or noncommunicable disease initiatives, can enhance resource utilization and program scalability. Implementing lung cancer screening in resource-limited settings requires strategic investment, capacity building, and policy interventions that prioritize equity. Addressing financial constraints, infrastructure gaps, and sociocultural barriers can help overcome existing challenges. By focusing on cost-effective strategies, public awareness, and risk-based eligibility criteria, global efforts can promote equitable access to lung cancer screening and improve outcomes.  Lastly, as part of the medical community, we play an important role in a patient's decision to pursue lung cancer screening. Being up to date with current lung cancer screening recommendations, identifying eligible patients, and encouraging a patient to undergo screening often is the difference-maker. Electronic medical record (EMR) systems and reminders are helpful in this regard, but relationship building and a recommendation from a trusted provider are really essential here. Dr. Nate Pennell: I think that makes a lot of sense. I mean, there are technology improvements. For example, our lung cancer screening program at The Cleveland Clinic, a few years back, we finally started an automated best practice alert in our EMR for patients who met the age and smoking requirements, and it led to a six-fold increase in people referred for screening. But at the same time, there's a difference between just getting this alert and putting in an order for lung cancer screening and actually getting those patients to go and actually do the screening and then follow up on it. And that, of course, requires having that relationship and discussion with the patient so that they trust that you have their best interests. Dr. Cheryl Czerlanis: Exactly. I think that's important. You know, certainly, while technology can aid in bringing patients in, there really is no substitute for trust-building and a personal relationship with a provider. Dr. Nate Pennell: I know that there are probably multiple examples within the U.S. where health systems or programs have put together, I would say, quality improvement projects to try to increase lung cancer screening and working with their community. There's one in particular that you discuss in your paper called the "End Lung Cancer Now" initiative. I wonder if you could take us through that. Dr. Cheryl Czerlanis: Absolutely. "End Lung Cancer Now" is an initiative at the Indiana University Simon Comprehensive Cancer Center that has the vision to end suffering and death from lung cancer in Indiana through education and community empowerment. We discuss this as a paradigm for how community engagement is important in building and scaling a lung cancer screening program.  In 2023, the "End Lung Cancer Now" team decided to focus its efforts on scaling and transforming lung cancer screening rates in Indiana. They developed a task force with 26 experts in various fields, including radiology, pulmonary medicine, thoracic surgery, public health, and advocacy groups. The result of this work is an 85-page blueprint with key recommendations that any system and community can use to scale lung cancer screening efforts. After building strong infrastructure for lung cancer screening at Indiana University, they sought to understand what the priorities, resources, and challenges in their communities were. To do this, they forged strong partnerships with both local and national organizations, including the American Lung Association, American Cancer Society, and others. In the first year, they actually tripled the number of screening low-dose CTs performed in their academic center and saw a 40% increase system-wide. One thing that I think is the most striking is that through their community outreach, they learned that most people prefer to get medical care close to home within their own communities. Establishing a way to support the local infrastructure to provide care became far more important than recruiting patients to their larger system.  In exciting news, "End Lung Cancer Now" has partnered with the IU Simon Comprehensive Cancer Center and IU Health to launch Indiana's first and only mobile lung screening program in March of 2025. This mobile program travels around the state to counties where the highest incidence of lung cancer exists and there is limited access to screening. The mobile unit parks at trusted sites within communities and works in partnership, not competition, with local health clinics and facilities to screen high-risk populations. Dr. Nate Pennell: I think that sounds like a great idea. Screening is such an important thing that it doesn't necessarily have to be owned by any one particular health system for their patients. I think. And I love the idea of bringing the screening to patients where they are. I can speak to working in a regional healthcare system with a main campus in the downtown that patients absolutely hate having to come here from even 30 or 40 minutes away, and they'd much rather get their care locally. So that makes perfect sense.  So, under the current guidelines, there are certainly things that we can do to try to improve capturing the people that meet those. But are those guidelines actually capturing enough patients with lung cancer to make a difference? There certainly are proposals within patient advocacy communities and even other countries where there's a large percentage of non-smokers who perhaps get lung cancer. Can we expand beyond just older, current and heavy smokers to identify at-risk populations who could benefit from screening? Dr. Cheryl Czerlanis: Yes, I think we can, and it's certainly an active area of research interest. We know that tobacco is the leading cause of lung cancer worldwide. However, other risk factors include secondhand smoke, family history, exposure to environmental carcinogens, and pulmonary diseases like COPD and interstitial lung disease. Despite these known associations, the benefit of lung cancer screening is less well elucidated in never-smokers and those at risk of developing lung cancer because of family history or other risk factors. We know that the eligibility criteria associated with our current screening guidelines focus on age and smoking history and may miss more than 50% of lung cancers. Globally, 10% to 25% of lung cancer cases occur in never-smokers. And in certain parts of the world, like you mentioned, Nate, such as East Asia, many lung cancers are diagnosed in never-smokers, especially in women. Risk-prediction models use specific risk factors for lung cancer to enhance individual selection for screening, although they have historically focused on current or former smokers.  We know that individuals with family members affected by lung cancer have an increased risk of developing the disease. To this end, several large-scale, single-arm prospective studies in Asia have evaluated broadening screening criteria to never-smokers, with or without additional risk factors. One such study, the Taiwan Lung Cancer Screening in Never-Smoker Trial, was a multicenter prospective cohort study at 17 medical centers in Taiwan. The primary outcome of the TALENT trial was lung cancer detection rate. Eligible patients aged 55 to 75 had either never smoked or had a light and remote smoking history. In addition, inclusion required one or more of the following risk factors: family history of lung cancer, passive smoke exposure, history of TB or COPD, a high cooking index, which is a metric that quantifies exposure to cooking fumes, or a history of cooking without ventilation. Participants underwent low-dose CT screening at baseline, then annually for 2 years, and then every 2 years for up to 6 years. The lung cancer detection rate was 2.6%, which was higher than that reported in the NLST and NELSON trials, and most were stage 0 or I cancers. Subsequently, this led to the Taiwan Early Detection Program for Lung Cancer, a national screening program that was launched in 2022, targeting 2 screening populations: individuals with a heavy history of smoking and individuals with a family history of lung cancer.  We really need randomized controlled trials to determine the true rates of overdiagnosis or finding cancers that would not lead to morbidity or mortality in persons who are diagnosed, and to establish whether the high lung detection rates are associated with a decrease in lung cancer-related mortality in these populations. However, the implementation of randomized controlled low-dose CT screening trials in never-smokers has been limited by the need for large sample sizes, lengthy follow-up, and cost.  In another group potentially at higher risk for developing lung cancer, the role of lung cancer screening in individuals who harbor germline pathogenic variants associated with lung cancer also needs to be explored further. Dr. Nate Pennell: We had this discussion when the first criteria came out because there have always been risk-based calculators for lung cancer that certainly incorporate smoking but other factors as well and have discussion about whether we should be screening people based on their risk and not just based on discrete criteria such as smoking. But of course, the insurance coverage for screening, you have to fit the actual criteria, which is very constrained by age and smoking history. Do you think in the U.S. there's hope for broadening our screening beyond NLST and NELSON criteria? Dr. Cheryl Czerlanis: I do think at some point there is hope for broadening the criteria beyond smoking history and age, beyond the criteria that we have typically used and that is covered by insurance. I do think it will take some work to perhaps make the prediction models more precise or to really understand who can benefit. We certainly know that there are many patients who develop lung cancer without a history of smoking or without family history, and it would be great if we could diagnose more patients with lung cancer at an earlier stage. I think this will really count on there being some work towards trying to figure out what would be the best population for screening, what risk factors to look for, perhaps using some new technologies that may help us to predict who is at risk for developing lung cancer, and trying to increase the group that we study to try and find these early-stage lung cancers that can be cured. Dr. Nate Pennell: Part of the reason we, of course, try to enrich our population is screening works better when you have a higher pretest probability of actually having cancer. And part of that also is that our technology is not that great. You know, even in high-risk patients who have CT scans that are positive for a screen, we know that the vast majority of those patients with lung nodules actually don't have lung cancer. And so you have to follow them, you have to use various models to see, you know, what the risk, even in the setting of a positive screen, is of having lung cancer.  So, why don't we talk about some newer tools that we might use to help improve lung cancer screening? And one of the things that everyone is super excited about, of course, is artificial intelligence. Are there AI technologies that are helping out in early detection in lung cancer screening? Dr. Cheryl Czerlanis: Yes, that's a great question. We know that predicting who's at risk for lung cancer is challenging for the reasons that we talked about, knowing that there are many risk factors beyond smoking and age that are hard to quantify. Artificial intelligence is a tool that can help refine screening criteria and really expand screening access. Machine learning is a form of AI technology that is adept at recognizing patterns in large datasets and then applying the learning to new datasets. Several machine learning models have been developed for risk stratification and early detection of lung cancer on imaging, both with and without blood-based biomarkers. This type of technology is very promising and can serve as a tool that helps to select individuals for screening by predicting who is likely to develop lung cancer in the future.  A group at Massachusetts General Hospital, represented in our group for this paper by my co-authors, Drs. Fintelmann and Chang, developed Sybil, which is an open-access 3D convolutional neural network that predicts an individual's future risk of lung cancer based on the analysis of a single low-dose CT without the need for human annotation or other clinical inputs. Sybil and other machine learning models have tremendous potential for precision lung cancer screening, even, and perhaps especially, in settings where expert image interpretation is unavailable. They could support risk-adapted screening schedules, such as varying the frequency and interval of low-dose CT scans according to individual risk and potentially expand lung cancer screening eligibility beyond age and smoking history. Their group predicts that AI tools like Sybil will play a major role in decoding the complex landscape of lung cancer risk factors, enabling us to extend life-saving lung cancer screening to all who are at risk. Dr. Nate Pennell: I think that that would certainly be welcome. And as AI is working its way into pretty much every aspect of life, including medical care, I think it's certainly promising that it can improve on our existing technology.  We don't have to spend a lot of time on this because I know it's a little out of scope for what you covered in your paper, but I'm sure our listeners are curious about your thoughts on the use of other types of testing beyond CT screening for detecting lung cancer. I know that there are a number of investigational and even commercially available blood tests, for example, for detection of lung cancer, or even the so-called multi-cancer detection blood tests that are now being offered, although not necessarily being covered by insurance, for multiple types of cancer, but lung cancer being a common cancer is included in that. So, what do you think? Dr. Cheryl Czerlanis: Yes, like you mentioned, there are novel bioassays such as blood-based biomarker testing that evaluate for DNA, RNA, and circulating tumor cells that are both promising and under active investigation for lung cancer and multi-cancer detection. We know that such biomarker assays may be useful in both identifying lung cancers but also in identifying patients with a high-risk result who should undergo lung cancer screening by conventional methods. Dr. Nate Pennell: Anything that will improve on our rate of screening, I think, will be welcome. I think probably in the future, it will be some combination of better risk prediction and better interpretation of screening results, whether those be imaging or some combination of imaging and biomarkers, breath-based, blood-based. There's so much going on that it is pretty exciting, but we're still going to have to overcome the stigma and lack of public support for lung cancer screening if we're going to move the needle. Dr. Cheryl Czerlanis: Yes, I think moving the needle is so important because we know lung cancer is still a very morbid disease, and our ability to cure patients is not where we would like it to be. But I do believe there's hope. There are a lot of motivated individuals and groups who are passionate about lung cancer screening, like myself and my co-authors, and we're just happy to be able to share some ways that we can overcome the challenges and really try and make an impact in the lives of our patients. Dr. Nate Pennell: Well, thank you, Dr. Czerlanis, for joining me on the By the Book Podcast today and for all of your work to advance care for patients with lung cancer. Dr. Cheryl Czerlanis: Thank you, Dr. Pennell. It's such a pleasure to be with you today. Thank you. Dr. Nate Pennell: And thank you to our listeners for joining us today. You'll find a link to Dr. Czerlanis' article in the transcript of this episode.  Please join us again next month for By the Book's next episode and more insightful views on topics you'll be hearing at the education sessions from ASCO meetings throughout the year, and our deep dives on approaches that are shaping modern oncology. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:     Dr. Nathan Pennell    @n8pennell   @n8pennell.bsky.social Dr. Cheryl Czerlanis Follow ASCO on social media:     @ASCO on X (formerly Twitter)     ASCO on Bluesky    ASCO on Facebook     ASCO on LinkedIn     Disclosures:    Dr. Nate Pennell:        Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron       Research Funding (Institution): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi    Dr. Cheryl Czerlanis: Research Funding (Institution): LungLife AI, AstraZeneca, Summit Therapeutics

Mumbai markets are leading the global pack — but can sky-high valuations in cement and defense stocks hold? Hosted by Michelle Martin with Ryan Huang, we unpack India’s stunning 10% rally and what’s driving the bull run. JPMorgan’s bullish on beaten-down biotech: hear why Eli Lilly, Gilead, Merck, Regeneron, and Bristol Myers are back on their radar. DocuSign gets punished despite strong earnings — what’s spooking investors? Keppel DC REIT climbs back into the STI on AI-data centre bets, while Hello Kitty’s parent Sanrio outpaces Toyota. Plus, the Straits Times Index movers: CDL, Yangzijiang, and DFI Retail. See omnystudio.com/listener for privacy information.

Concluding their three-episode series filmed live in Chicago, your hosts wrap up the weekend with a discussion of the key bladder cancer presentations from the 2025 ASCO Annual Meeting. They begin in the perioperative space, reviewing updated CREST data presented since AUA and revisiting the NIAGARA trial last seen at ESMO 2024, and end by covering the latest EV-302 updates in the metastatic setting.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

Karl and Erum sit down with Erika Milczek, CEO and founder of Curie Co, to explore how synthetic biology is rewriting the rules of modern chemistry. Erika, a former Merck chemist, shares her journey from Big Pharma to launching a biotech startup that engineers enzymes to replace legacy chemicals in personal care and consumer goods. With insights grounded in regulatory shifts, manufacturing scalability, and the power of directed evolution, Erika discusses how her team is building a “biotech alternative to petroleum-based chemistry.” Whether you're curious about enzyme engineering, bioindustrial startups, or how synthetic biology can drive sustainability in everyday products, this episode delivers a high-energy, deeply technical, and inspiring dive into the future of materials innovation.Grow Everything brings the bioeconomy to life. Hosts Karl Schmieder and Erum Azeez Khan share stories and interview the leaders and influencers changing the world by growing everything. Biology is the oldest technology. And it can be engineered. What are we growing?Learn more at ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.messaginglab.com/groweverything⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Chapters:00:00:00 - Welcome to the Future: Setting the Stage00:00:22 - Juggling Labs, Life, and Launchpads00:01:27 - Terraforming Mars? Let's Dream Big00:04:58 - Joe Rogan, Speciation, and Sci-Fi Tangents00:10:08 - Biotech Beauty Week: Innovation on Display00:14:13 - Meet Erika Milczek: Enzymes Over Everything00:33:03 - Feeding the Bug: The Spark Behind Discovery00:35:15 - Scaling Science: What Makes Commercialization Hard00:35:51 - Why Partnerships Make or Break Biotech00:38:02 - Following the Rules: Regulatory Shifts & Product Strategy00:42:48 - From the Lab to RTP: Building in Biotech's Backyard00:45:37 - Ecosystem First: How to Build Bio Economies00:50:01 - Fundraising Real Talk: Investors, Guts & Growth00:53:50 - Biomanufacturing Is Just Getting Started00:56:29 - Let's Talk Packaging: Biotech's Next Frontier00:59:52 - Wrapping Up: Lessons, Hope, and What's NextLinks and Resources:Curie CoMars: One Day on the Red Planet (film)Marsbound by Joe Haldeman (book) The case for Mars terraforming research (Erika de Benedicts research paper)Ben Lamm on Joe Rogan ExperienceDire Wolf on the cover to Time MagazineSupplier's Day 2025 during Messaginglab's unofficial Biotech Beauty WeekCapsum - microfluidics contract manufacturingP2 company - conditioning agents⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Topics Covered: biomanufacturing, cell free biomanufacturing, enzymes, nutraceuticals, biotech, pharmaceuticals, AI, spinoutsHave a question or comment? Message us here:Text or Call (804) 505-5553 ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Instagram⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠  / ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Twitter⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ / ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠LinkedIn⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ / ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Youtube⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ / ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Grow Everything⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Email: groweverything@messaginglab.comMusic by: NihiloreProduction by: Amplafy Media

Picking up from Episode 23, your hosts turn their focus to the highly anticipated prostate cancer presentations from the 2025 ASCO Annual Meeting in Chicago. They begin with a discussion on mCSPC, focusing on the AMPLITUDE trial, followed by results from TALAPRO-2, the ARANOTE trial, IRONMAN, and STAMPEDE. The episode wraps with key abstracts and oral presentations on mCRPC.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in the Pharma and Biotech world.Jefferies predicts an increase in small tuck-in deals in the biotech industry as companies face challenges accessing capital. Companies and industry groups are offering solutions to mitigate the impact of Trump tariffs on rare disease, cell, and gene therapy. Pitchbook suggests a shift towards more sustainable investing in biotech VC firms. Gilead is gearing up to challenge J&J in the $20 billion multiple myeloma CAR-T market. PTP's generative AI is revolutionizing data summaries for biotech QC workflows. Sanofi recently acquired Blueprint for $9.5 billion, while BMS has committed up to $11 billion with Biontech. Lilly has signed a deal worth up to $870 million, and Regeneron is investing nearly $2 billion in a Chinese obesity drug. Merck's CEO is emphasizing diversity in operations following the defeat of an anti-DEI measure. Immuno-oncology drugs Keytruda and Opdivo may face scrutiny in the near future.In other news, Vigil Neuroscience's Trem2 antibody for a rare brain disease failed in a Phase II trial shortly after Sanofi's acquisition of the company. Analysts believe the results were not surprising and should not impact the deal. Lilly has signed a deal worth up to $870 million to develop a long-acting GLP-1 obesity drug, while the FDA is committed to making rare disease drugs available at the first sign of promise. Pharma tuck-in deals are increasing after a slow first quarter for small biotechs. BioAgc Biologics will be attending Bio International in Boston to discuss their global drug production capabilities.Stay tuned for more updates on investing in research, welcoming global talent, the biotech VC cycle, Gilead's challenge to J&J in the multiple myeloma CAR-T market, and much more. Upcoming events and job listings in the pharmaceutical industry are also featured in our newsletter.Thank you for tuning in to Pharma and Biotech daily.

Recorded live in Chicago, your hosts explore the latest in kidney cancer, discussing new five-year follow-up data from KEYNOTE-564, the long-term results of CheckMate 214, insights from the ongoing PDIGREE trial, and much more.The View on GU with Lalani & Wallis integrates key clinical data from major conferences and high impact publications, sharing meaningful take home messages for practising clinicians in the field of genitourinary (GU) cancers. Learn more about The View on GU: theviewongu.caThis podcast has been made possible through unrestricted financial support by Novartis, Bayer, Astellas, Tolmar, Ipsen, J&J, Merck, Pfizer, Eisai and AbbVie.

In this dynamic episode, Meredith joins us to discuss how to create presentations that resonate deeply with your audience. Discover her expert tips on simplifying complex ideas, leveraging storytelling to inspire action, and ensuring your message stands out—whether you're presenting on stage, in meetings, or on camera.Meridith Grundei is a dynamic public speaking coach and innovative experience architect dedicated to helping leaders and entrepreneurs transform complex ideas into compelling, memorable presentations. Drawing from her extensive background in theater and improv, Meridith uniquely combines creativity, clarity, and authentic connection to empower clients to confidently command the stage and inspire action.As the founder of Grundei Coaching, Meridith has partnered with global industry leaders such as Google, Merck, Amazon AWS, and Pfizer, alongside numerous visionary entrepreneurs and professional teams. Renowned for her engaging, collaborative style, Meridith has successfully guided thousands of professionals to deliver impactful presentations, build meaningful connections, and elevate their overall communication effectiveness.Meredith also reveals how incorporating improvisation techniques into your training sessions can enhance your ability to think quickly, build genuine connections, and communicate with confidence and authenticity.Creativity isn't confined to artistic pursuits—it's transformative in business, driving innovation, problem-solving, and impactful communication. Whether you're an experienced speaker or new to presenting, this conversation equips you with powerful tools to express yourself clearly, creatively, and memorably.Connect with Meridith:https://www.linkedin.com/in/meridith/https://members.confidentlyspeaking.fun/Learn more about our Lyrics 'N Leadership Institute launch which is today May 28th, 2025 here: https://lyricsnleadership.org/   Listen to more episodes on Mission Matters:https://missionmatters.com/author/genein-letford/

Hier geht's zur Warteliste für das Kinderdepot. Aktien + Whatsapp = Hier anmelden. Lieber als Newsletter? Geht auch. Das Buch zum Podcast? Jetzt lesen. Meta kauft Atomkraft von Constellation. Toyota kauft Toyota mit Toyoda. Hims & Hers kauft Zava. Merck scheitert beim MoonLake-Kauf. Sonst hatte Dollar General gute Zahlen. Wozu auf die Marinesparte von Thyssenkrupp warten, wenn man Kongsberg (WKN: 888818) hat? Irgendwas zwischen SpaceX, Accenture und Rheinmetall. Das ist Indra Sistemas (WKN: 873570). Diesen Podcast vom 04.06.2025, 3:00 Uhr stellt dir die Podstars GmbH (Noah Leidinger) zur Verfügung.

S&P futures are pointing lower today, down (0.47%). European equity markets are firmer, following slightly weaker levels on Monday. Asian equity markets went mostly higher, with Hang Seng a notable outperformer. Overnight, US 2-year yield down 1 bps to 3.9% and 10-year down 3 bps to 4.4%. Dollar firmer, oil up, gold down, industrial metals lower. Renewed US-China trade tensions has spilled into public view with both sides accusing each other of reneging on Geneva deal. White House talking up prospects of a Trump-Xi call this week but no confirmation yet from China. Critical minerals remain source of tensions with China reportedly slow walking offer to relax rare earths curbs, a response to latest US tech curbs and revocation of Chinese student visas. Companies Mentioned: Snowflake, Merck, Crunchy Data, MoonLake Immunotherapeutics

In der heutigen Folge sprechen die Finanzjournalisten Anja Ettel und Holger Zschäpitz über eine Schreckensnachricht für Tesla-Aktionäre, einen neuen Rüstungs-ETF und gute Nachrichten vom IPO-Markt. Außerdem geht es um Bristol Myers Squibb, Pfizer, Summit Therapeutics, InstilBio, Rheinmetall, Hensoldt, Leonardo, BNP Paribas Easy Bloomberg Europe Defense ETF (WKN: A417F7), BNP Paribas Easy MSCI World Equal Weight Select ETF (WKN: A417BH), Invesco MSCI World Equal Weight ETF (WKN: A40G12), Xtrackers MSCI World ex USA (WKN: DBX0VH), Circle, BAE Systems, Saab, SAP, Merck, Salzgitter, Thyssenkrupp, Voestalpine und ArcelorMittal, Steel Dynamics, Nucor, Gerresheimer, Kongsberg Gruppen, Safran, Airbus, Rolls Royce, Leonardo, QinetiQ, Steyr Motors. Wir freuen uns an Feedback über aaa@welt.de. Noch mehr "Alles auf Aktien" findet Ihr bei WELTplus und Apple Podcasts – inklusive aller Artikel der Hosts und AAA-Newsletter.[ Hier bei WELT.](https://www.welt.de/podcasts/alles-auf-aktien/plus247399208/Boersen-Podcast-AAA-Bonus-Folgen-Jede-Woche-noch-mehr-Antworten-auf-Eure-Boersen-Fragen.html.) [Hier] (https://open.spotify.com/playlist/6zxjyJpTMunyYCY6F7vHK1?si=8f6cTnkEQnmSrlMU8Vo6uQ) findest Du die Samstagsfolgen Klassiker-Playlist auf Spotify! Disclaimer: Die im Podcast besprochenen Aktien und Fonds stellen keine spezifischen Kauf- oder Anlage-Empfehlungen dar. Die Moderatoren und der Verlag haften nicht für etwaige Verluste, die aufgrund der Umsetzung der Gedanken oder Ideen entstehen. Hörtipps: Für alle, die noch mehr wissen wollen: Holger Zschäpitz können Sie jede Woche im Finanz- und Wirtschaftspodcast "Deffner&Zschäpitz" hören. Außerdem bei WELT: Im werktäglichen Podcast „Das bringt der Tag“ geben wir Ihnen im Gespräch mit WELT-Experten die wichtigsten Hintergrundinformationen zu einem politischen Top-Thema des Tages. +++ Werbung +++ Du möchtest mehr über unsere Werbepartner erfahren? [**Hier findest du alle Infos & Rabatte!**](https://linktr.ee/alles_auf_aktien) Impressum: https://www.welt.de/services/article7893735/Impressum.html Datenschutz: https://www.welt.de/services/article157550705/Datenschutzerklaerung-WELT-DIGITAL.html

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Regeneron's shares have dropped due to the failure of their dupixent follow-up drug, while Sanofi has acquired Blueprint for $9.5 billion to expand their rare disease portfolio. Bristol Myers Squibb is collaborating with Biontech on a bispecific antibody for solid tumors, and Amgen's imdelltra has shown a 40% increase in survival for small cell lung cancer at ASCO. Moderna has received FDA approval for their next-gen COVID-19 vaccine, and AstraZeneca is partnering with AI companies to stop cancer at all stages. Keros has cut 45% of its workforce along with a pulmonary hypertension drug, and Jazz has presented new cancer data at ASCO. FDA actions are pending for companies like Merck, Gilead, and Regeneron/Sanofi.The implications of the overturning of the FDA's lab-developed tests rule in a post-Chevron legal landscape are discussed, where power has shifted from federal agencies to the courts. Upcoming FDA decisions, including Gilead's HIV prophylaxis lenacapavir, are highlighted, along with new FDA guidelines on nitrosamine testing for the pharmaceutical industry. Jazz Pharmaceuticals is in the "goldilocks zone" with new cancer data at ASCO25, showcasing results from acquisitions made over the past five years. Zeiss introduces an AI-powered spatial biology solution for research labs. Other news includes updates from ASCO25, cell and gene therapy developments, and upcoming events in the biopharma industry.

Why do technical experts often make poor change leaders? Roger Guerrero, Head of Enterprise Strategy Execution at Merck, challenges how organizations select and develop leaders in transformation environments. Drawing from his experience overseeing Merck's corporate strategy implementation, Roger explains why change leadership shouldn't be confined to specialized teams but embedded as a core expectation for all managers. He argues that companies over-index on technical expertise while undervaluing the ability to inspire and lead through change—creating what he calls a "silent killer" in organizations. Whether you're struggling with resistant middle managers or disconnected executives, Roger offers practical strategies for identifying and developing genuine change leadership beyond technical competence.----Connect with:⁠⁠⁠⁠⁠⁠⁠⁠Nellie Wartoft⁠⁠⁠⁠⁠⁠⁠⁠CEO of ⁠⁠⁠⁠⁠⁠⁠⁠Tigerhall⁠⁠⁠⁠⁠⁠⁠⁠Chair of the ⁠⁠⁠⁠⁠⁠⁠⁠Executive Council for Leading Change (ECLC)⁠⁠⁠⁠⁠⁠⁠⁠nellie@tigerhall.com ----00.00 - Introduction 01:30 - Why change management shouldn't be limited to specialized teams03:45 - How technical industries often select leaders for technical expertise, not leadership ability05:20 - Why change leadership competencies should be core criteria in promotions07:10 - The problem with the "individual contributor to leader" career path09:15 - Creating dual career tracks for technical experts vs. leadership roles11:30 - How to identify people with natural change leadership abilities14:45 - Addressing the "this isn't my job" mindset in middle managers16:20 - Red flags that indicate poor change leadership potential19:40 - The evolving profile of effective senior leaders—from engineers to MBAs to motivators22:15 - Strategies for working around resistant leaders you can't replace24:30 - Handling resistance at the C-suite level27:15 - The importance of communication style in successful change initiatives29:35 - Why transparency and empathy are critical for change leadership----Breathe by RYGO | https://soundcloud.com/francesco-rigolonEverything You Need Is By Your Side by Vlad Gluschenko |Music promoted by https://www.free-stock-music.comCreative Commons / Attribution 3.0 Unported License (CC BY 3.0)https://creativecommons.org/licenses/by/3.0/deed.en_US

Constellation Energy, Merck, Mattel, Dollar General, NIO y CloudeStrike, bajo la lupa de Rafael Ojeda, analista independiente.

Highlights from AUA2025: Advances in NMIBC (2025) CME Available: https://auau.auanet.org/node/43167 At the conclusion of this CME activity, participants will be able to: 1. Recognize recent developments in the management of NMIBC. 2. Evaluate new and emerging therapies for NMIBC, such as novel intravesical agents and immunotherapies, their mechanism of action and related adverse events. 3. Employ current management approaches for NMIBC. 4. Utilize risk stratification to guide treatment decisions for NMIBC patients. 5. Implement diagnostic techniques for NMIBC, including cystoscopy, urine cytology, biomarkers, and advanced imaging modalities. This educational activity is supported by independent educational grants from: Merck & Co., Inc. ImmunityBio, Inc.

Dr. Shalabh Gupta, founder and CEO of Unicycive Therapeutics, shares his inspiring journey from practicing medicine to leading groundbreaking innovations in kidney disease treatment. Dr. Gupta discusses his comprehensive framework for identifying and developing medical solutions, his vision for Unicycive's future, and the importance of focus and execution in medical startups. He reveals the challenges and triumphs of bringing life-changing products to market and offers profound advice for new entrepreneurs in the industry.   Guest links: https://unicycive.com/  Charity supported: Feeding America Interested in being a guest on the show or have feedback to share? Email us at theleadingdifference@velentium.com.  PRODUCTION CREDITS Host: Lindsey Dinneen Editing: Marketing Wise Producer: Velentium   EPISODE TRANSCRIPT Episode 056 - Dr. Shalabh Gupta [00:00:00] Lindsey Dinneen: Hi, I'm Lindsey and I'm talking with MedTech industry leaders on how they change lives for a better world. [00:00:09] Diane Bouis: The inventions and technologies are fascinating and so are the people who work with them. [00:00:15] Frank Jaskulke: There was a period of time where I realized, fundamentally, my job was to go hang out with really smart people that are saving lives and then do work that would help them save more lives. [00:00:28] Diane Bouis: I got into the business to save lives and it is incredibly motivating to work with people who are in that same business, saving or improving lives. [00:00:38] Duane Mancini: What better industry than where I get to wake up every day and just save people's lives. [00:00:42] Lindsey Dinneen: These are extraordinary people doing extraordinary work, and this is The Leading Difference. Hello, and welcome back to another episode of The Leading Difference podcast. I'm your host, Lindsey, and today I am so excited to introduce you to my guest, Dr. Shalabh Gupta. Dr. Gupta is the founder and CEO of Unicycive Therapeutics. He is a visionary in healthcare, leading groundbreaking efforts to design innovative therapies and reimagine how we approach unmet medical needs. His work goes beyond the lab as he's driving a healthcare revolution by developing innovative therapies addressing critical gaps in treatment. His perspective combines decades of experience and expertise in drug design with a deep commitment to equity in health care. Well, welcome to the show, Shalabh. I'm so excited that you're here with me today. [00:01:35] Dr. Shalabh Gupta: Thank you. Thank you for hosting me. [00:01:36] Lindsey Dinneen: Of course. I'd love if you wouldn't mind just telling us a little bit about yourself, your background, and what led you to MedTech. [00:01:45] Dr. Shalabh Gupta: By way of background, I'm a physician, trained, practiced, did my medical training in internal medicine, residency in physical medicine and rehab, research fellowship in cardiac and pulmonary rehabilitation, board certified physician, practice in New York at NYU hospital, NYU Medical Center. This is where I did my medical training for roughly decade after finishing medical school. I also have a graduate degree in finance management from NYU. While I was doing my residency training, I realized that I wanted to find a way to have a broader impact on society as well as what we were working on in learning medicine. So, I started my career working initially with a biotechnology company at the time to help them get their drug with FDA through a regulatory approval process. The beginning of the process is called IND following a investigation new drug application, IND application. I actually visited FDA on their behalf, met with FDA back in the time when everything used to be in person. Built from there onward, joined Wall Street from working as a stock analyst. So I covered biotech companies as a stock analyst, and the weekend and holidays that were available, I worked to continue to practice the medicine at NYU as an attending physician, and then joined another bank and covered pharmaceutical stocks and worked covering six of the largest pharma companies that include Pfizer, Merck, Viacom, Selling Power, Eli Lilly, Bristol Myers Squibb. From there, I moved to California. I worked for Genentech in corporate strategy. Genentech, at the time, and continues to be, one of the largest biotechnology companies. And from working at Genentech, I got my inspiration to start my own companies. So I founded two companies prior to finding starting Unicycive. All my companies are focused on aesthetic therapeutic area. Unicycive is focused on nephrology, treatment of kidney diseases, and we have two drugs in development. We have a lead drug that is pending approval from the US FDA in June of 2025 this year. And the second, I guess, finish phase 1 clinical trial in the UK. And we are in discussion with the agency to proceed with the next stage of clinical trial in the US. So that's a quick background. [00:04:14] Lindsey Dinneen: Wow. That's incredible. Thank you for sharing your story. Yeah. So let's talk about your company now. You've become CEO of this company. You're developing these products that are going to change lives. What first made you realize that there was a gap that needed to be filled in the market for this? And then, what prompted you to go, "You know what? Hey, I think I can have the solution for this or I can have the answer to this." [00:04:38] Dr. Shalabh Gupta: The first question that you ask, understanding the unmet need in medicine, there are a lot of problems that you can address. So, to give you a framework, if I am thinking about a problem, I want to understand if a couple of things, and in order of priorities, these are: can I find a solution that with my resources-- resources is time, energy, and money-- can I create a product that will truly make it to the market? Number two is that I also feel that one can get very blindsided that "I have a solution," but not understand what other solutions exist in the market. So understanding the competitive landscape. If I create this drug, this device, this product, and it is going to take three to four years in the market to come to the market-- which, by the way, in medical word is a still very fast track because it takes much longer-- what will the competitive landscape look like for 5 years down the road? So that's the second part. And third is that what is the solution that I'm developing? Is it unique in terms of having a novel, either as a drug device or drug device combination, or as a patented drug, patented device, because in our industry, it's not really possible to scale up something until unless you have an IP or intellectual property protection. And then from there onward, the last thing is also, who's going to fund me, how I think about funding, not for next six months a year, but also a continuum of the product development. If I think about all these 4-5 problems, then you start to narrow it down. There are some problems that are very much worthy of exploration. For example, treatment of Alzheimer's, we all know it's a big unmet need, we all know there's a big market opportunity. But I realized that was something we couldn't do it with the products or the development candidates that I had seen. So, being able to define where is the end point and goal. Being able to understand, can I make an impact? And when I say I, I speak for myself, but each one of us, I always remind entrepreneurs, we each one of us have our own deck of cards. We have to play with our cards, we can't compare ourselves with somebody else, or we can compare some other cases study. So understanding more about what is so unique that I can bring to table that can I make a difference and then making a business around this where the thesis lies. Once you identify that, then there's a question about continuing to execute and keep changing your plan as you go along. [00:07:11] Lindsey Dinneen: Yeah, absolutely. Well, I love your framework for thinking through all of those things. And so of course you use that when you thought, "Hey, here's this issue. I could potentially have a solution," and you went through this process. And then can you tell us about your innovation now and how that is helping and how you expect it to help change all these wonderful lives? [00:07:33] Dr. Shalabh Gupta: So, so for treatment of kidney diseases, first of all, it has been one area of development that has not had that much of innovation. And, and I think that is where the initial part of the thesis was that focusing on nephrology of kidney diseases is not same as developing a drug for cancer treatment. Cancer treatment changes every six months a year. The standard of care continues to evolve. Is there an unmet need in cancer treatment? A hundred percent, but the part is that the pace of innovation is very rapid. Is it same in nephrology? It's getting there, but it's still the development of a new products in nephrology still is not at the same pace. So I thought there was something we could make a difference by a small company. The drug that I acquired from another company was a drug that had finished a clinical trial. So it had shown that the drug is safe. It had also shown some signal of it working in healthy volunteers. That's a phase one trial. And the innovation came from a car battery company that had figured out how to make a big, large size pill to make it smaller. And sometimes greatest innovation, greatest insight come from the fact that when I talk to the kidney doctors, the physicians who take care of these patients there with the treatment of kidney diseases, they said the problem for these patients are the patients have to take 12 to 15 pills per day. And this innovation allowed us to be able to make that number of pills go down from 13 to 12 or 15 to three pills per day, one pill with each meal. And then the regulatory pathway became a bit more clear that if I can show that our drug is similar to the drug that was in the market, maybe there was an opportunity to go through expedited pathway, which is what we did. And I acquired the drug in 2018, went to FDA right after acquiring the drug to expedite the pathway again, thinking about de risking the development pathway. And as I mentioned in 2025, we are expecting the approval. So that is the process about it. And that's the story behind the lead drug. [00:09:51] Lindsey Dinneen: Great. Excellent. So that is really exciting. And as you continue to go forward with this company and the innovations that you're creating, what is your ultimate goal or dream that you're really striving for? [00:10:06] Dr. Shalabh Gupta: So, the focus for Unicycive is building new novel treatment for kidney diseases. Our lead drug is expecting approval in June 2025. But we have a second drug in development, and we continue to think about what will be something that we as a small company can bring to market. There are other areas of unmet need in kidney treatment. But instead of doing too many things at the same time, we continue to think, "How do we grow our company? What will be the vision for the company three years down the road, five years down the road?" And what we want to continue doing is to develop the drug candidates, advance them. Right now, after the first drug we get through approval, it will be the second drug. There is a thought process behind it. One of the biggest challenges that I've seen for smaller companies and startups is that they end up in doing too many things at the same time, which is difficult to do, even for big companies. You know, big companies, they have a one product that is a marquee product, they launch that and then they develop other things. So, being able to stay focused is also key because you can have a lot of energy, you can have a lot of ideas, but you have to focus on which one you can do first. [00:11:22] Lindsey Dinneen: Yeah, that is so true. It's such great advice, a good reminder. Yes, focus is so important. You know, honestly, that's probably one of the tricky things that startups in this particular field might struggle with is that focus. So I'm wondering what kind of advice do you have for say a brand new entrepreneur in the industry who has these great ideas, but you know, maybe has so many that they're a little too scattered. [00:11:52] Dr. Shalabh Gupta: Right. So, I think you may start with 10 ideas but the framework I gave you that: can this idea in this given timeframe with my resources and the funds that I can raise, can it make a difference? So you start to narrow it down. You start with a big funnel, narrow it down. And then maybe you have two or three ideas. Instead of thinking to yourself that "No, I'm not going to tell my idea to anyone because somebody else can take it away," find people who will be willing to pressure test those ideas. Then you will have identified something, maybe one Idea that is worth the pursuit. So then you focus on that. So that's one part of how to triage it because we all have ideas, but those ideas may not be worth developing once you go and talk to the marketplace. And marketplace is your investors, the physicians, and the patients. I keep saying about these three stakeholders, because if physicians cannot prescribe what you are developing, then it's of no use. If patients don't necessarily benefit, then it's of no use. And if you cannot get insurance companies a reimbursement for that means the product will never get here. So it's a process, but nobody can come up with an idea. And there is no great idea. There are ideas that you have to, and then once you find that one idea that resonates with all the stakeholders, physicians are excited about it. If you talk to patients, and you want to do that early on, you don't want to develop an idea and then go, you know, that is the greatest idea but nobody really perceives it that way that except you and a couple of your friends and people who work with you. I don't mean in a bad way. I mean, that you want to be able to test this idea very quickly. So once you get that idea, once you identify what is that the company should be focused on, then the question about is actually building an execution plan. And the only advice I can give is that at any given day for a company, startup, especially whether you're a founder or you're a founding team member, the list of priorities is 50, 5, 0, or maybe 100. It takes time to figure out of those 50, which are the top three that are most important and then being able to focus on those three. You know, the reason I say that no one can work on 50 priorities at the same time. But we all can take two or three priorities and say, "These are the three things that I'm going to work on today. That is this week. Those are the things I'm going to do this month." And therefore you start to develop identifying priorities. The right ones takes time. Sometimes it is a fundraising. Sometimes it's a building a team. Sometimes it's a product development. Sometimes it's all three of them, but being able to allocate your time and energy and focus is a key. People say it's the question of money. I don't think it's a question of money. Money is one of the resources, but the biggest resource we all have is a time and energy and focus. In a company of our size, we are a publicly listed company, and we now have grown from where we used to be, and it's still small. Even today, there are a lot of things we choose not to do. We choose not to go to conferences. We choose not to publish papers. If something is a priority to us, we say, "This is the only thing we're going to focus on. This is the next three months, this is our main goal." And every team meeting I have, I always remind people, three priorities. More than three, way too many. One may not be enough. But because if you can't remind people, what is the priority for the company, then you will not succeed. It is a very challenging environment to think about a startup company or companies in general. And when you have too many priorities, you tend to lose focus on. By building priorities, having priorities, executing them. You create momentum, you create confidence. They create success and you keep climbing the ladder. But truly the biggest challenge for us in the beginning of the career is that identifying which are those three priorities that matter. And once you have had some experience, then the challenge is to keep those priorities and change them as you go along, right? As you go along, you have to continue to grow. For example, in the beginning, it may be the five people you have and that may be enough. But as where we are in the company, it's a question about growth of the organization, right size, not too many people, not too little, hiring enough people so we can continue to execute on our vision and the promises that we made to ourself and to our investors. [00:16:27] Lindsey Dinneen: Thank you for that advice. That was fantastic. And such a great way to narrow it down and help people understand how to narrow down so that they can actually focus and succeed before moving on. I love that. Thank you. So, you know, looking back over your life, and of course, you've had such an incredible career that has really taken you in a lot of different directions. Could 10 year old you have ever anticipated where you'd be today? [00:16:54] Dr. Shalabh Gupta: I don't think so. I think I think we all have a what I call a true north compass. What I did think at the 10 years of age, if I can go back, maybe 10 is too early but maybe 15 or 16 or 17, that hasn't changed. Let me tell you 2 things that I always felt most inspired and excited about. Number one was that I wanted to be in healthcare because, intellectually, I like biological sciences. I felt, "My gosh, what could I do with that if I could make a difference?" And number two was that I, from very early on, I wanted to be something which could help people directly. As you know, there are many ways you can help people, but being in medicine or healthcare, I felt there was a direct impact. Now, looking back after several decades, I feel that part of the influence was my dad. My dad is a physician, continues to see patients and do pro bono work. So that had a very lasting influence on me. That helped me to think about, okay, this is what I want to do. Then being trained as a physician, then going to work on Wall Street, then there was a question about understanding how the impact can be broadened, if you will. The way to think about what I do today versus what I did, say, as a physician, physicians see, say, 10 patients, maybe 12 patients if you're seeing an outpatient basis per day. And if you're in an ICU or ICU doctor, an ER doctor, you could see more number of patients, but then smaller time. And you multiply that impact that many patients, let's just say 10 patients per day, and you work at 300, 350 days, 360 days, 365 days, don't take any break, but that is that many patients a year. What we do today has a potential to impact hundreds and thousands and millions of patients and not just in the U S, globally. So from one vantage point is just magnifying the impact. And the other vantage point is doing what I would have done before. I still love sciences every day. My job is to not just talk about business, but also think about, "How do we fundamentally solve the problem?" And having had those experiences you know, it helps you to keep yourself grounded. One part, I know this wasn't your question, but one advice I can give people who are thinking about developing their careers as an entrepreneur, if you are a founder and CEO, especially think about your career or skill set as I spoke, a wheel, a circle. Every skill that you have, some of us start with more technical background, like me and MD. Then you have to develop their finance and business skills and the business development skills. So sometimes people say, "Well, you know, ABC went to grad school and they dropped out of grad school and they started a company." That's wonderful, but think about much longer beyond a two-year, three-year, five-year time horizon. And that's what helped me to think about my career. So I worked on the Wall Street, but that gave me a finance and understanding about how public companies are valued, not just by the company, but how stock analysts value the company, how investors value the company, what moves the stock, what did Genentech to understood. That gave me the chance to understand how a big biopharma company thinks about their product development. And at Genentech, in some interactions we have had, we were looking at the products from other smaller companies, either to collaborate with them or to acquire those products. So that's a different skill set. I went very early on, as I said, in my career, I went to FDA. So even though I'm not regulatory expert, but I understand how agencies think about the product approval so that helps you to make a more of a holistic viewpoint because the business has become more complex, and you cannot just have a only business degree and you say, "Well, I'm going to succeed." Some people have rounded that up by years and years of experiences. And then there is also innate desire to learn. I learned from not just doing the work I do every day, but my, my, you know, talked a lot about it. I read anytime I get I read books that are not related to medicine, that are not necessarily related to health care, because you have to understand how to grow a revolution. You have to understand leadership skills that are not necessarily taught in schools. So, you have to find a way to continue to refine yourself, because the only way you can create a great company is to become a better version of yourself. [00:21:31] Lindsey Dinneen: Thank you so much for talking about that and for sharing your advice. And I love that image of the wheel. It's a good reminder that sometimes life takes you on very interesting tangents, but sometimes they all do merge at some point. You've got this little sliver of this knowledge that you're working on, and then this experience, and then they start building and I really love that, that, that way of thinking about it and also remembering that It's very useful. So, so like even earlier, I was struck, you talked about how there was inspiration from car batteries, right? And so how interesting is that to go from, what you might expect within your industry, here's how to solve a problem. But then you guys went outside and said, how do other people solve problems? Like maybe we can borrow from that. And I think that's really cool. [00:22:21] Dr. Shalabh Gupta: And I also think that if you stop focusing on only in your industry, learn from anywhere. Some of the best learnings that I have personally, that felt inspirational to me, did not come from biotech companies. They come from tech companies, truly. When you think about the worst, most successful tech companies like Amazon, Apple. I can go on and on, but there are things that you can learn from them. There are things you can learn from the founder of Amazon, Jeff Bezos. He talks about building Amazon and he talks about doing many experiments at a smaller scale that fail at Amazon in order for them to succeed at a few that really work. And this is where I was saying that culling the ideas, you may start with 10 ideas, but no one can develop 10 ideas, no one. And it's not because of money. People say, "Well, that if I had money." There have been numerous examples where companies have been funded with lots of money and the companies fail. Part of the problem is that when you get too much money, I think you may not realize that you still have to deliver. Because focus and execution takes really knowing what the target is, and then hitting the target and not one time and time again. Targets may change, but the companies cannot focus in 20 different things. In the beginning, you have to start with a very key thesis. [00:23:39] Lindsey Dinneen: Yeah. Absolutely. Absolutely. And yeah, so learning from other industries, and that actually kind of also brings up a thought. So as you've gone along in your career and you've had many different iterations of who you are and what you bring to the world, now, are there any moments that really stand out to you as affirming, "Yes, I am in the right place at the right time?" [00:24:04] Dr. Shalabh Gupta: Yeah, that's a very good question. And I have had a chance to think about it every now and then. So there are there, there are certain observations I'll make. You know, people always say, " What will be your dream job?" And I think the dream job for someone is the job that which you will do any given day, and you will feel a joy that you're doing it and you're not doing for remuneration. You're not doing because you're going to get paid. And we all have those different moments in time. People talk about "flow" where the time stops because you're doing something so deeply engaging that you lost track of time. You forgot where you are. You're not feeling tired. For me building of this company and the team that we have assembled at Unicycive is that flow. Any day that I'm not traveling, I am in my office. I don't work from home. I am every single day in my office. And sure we have a small team, but when we work with the team, these are motivated, driven people with decades of experiences. We feel that we are in a common mission, like we are solving the world's greatest problem. And I know that may be exaggeration, but that's how it feels. And being with them in a room and thinking about a complex problem-- and not just thinking of a problem like how big companies think about it-- but thinking of the problem in a scientific way, but delivering it a solution that only a small company can do that to me is a joy. Number two part is that as I've gone further on my career, I, I am a mentor to a number of startups from Stanford and UCSF, and many Stanford companies, many of them come with a very different problem than purely a biotech company. Since the pro bono work, I do this because I find by telling other people from their problem, I get to reflect on my own problem, and I do that on every quarter. There's one or two companies and I've been really privileged. I feel one of the greatest joys to meet with these great CEOs and Stanford has been a great collaborator. They have a program called Start X in which they have these companies that are participating in a accelerator program. And Stanford's accelerator is different and unique that they don't take any equity. They provide you the opportunity for mentorship. I was part of that program many years ago. So I meet with the CEOs and many of these CEOs will come very different problem. As an example, there is a company that's focused on artificial intelligence using interaction between a physician or healthcare provider and patient, and being able to use AI to streamline that interaction. That is a point that I saw of 10 years of clinical practice, how that communication is broken, literally is broken. Patients go to doctors, not because doctors are the world's greatest knowledge source, but patients at the end of day, they need someone to help them feel better, help them understand the problem that the physician can solve it. What ended up in being in today's healthcare system in the U. S. is that doctors have become mechanical and not because doctors are bad, because we are given these many things to document these many things to chart. If you talk to a physician, a primary care physician, many times the physician is sitting behind the computer screen. Those bedside manners are gone, like literally they are not there until you go into concierge medicine because the physician has to fill up this chart. I practice medicine. So understanding how this company and this CEO, this entrepreneur is trying to solve that problem, I lean back to the years of clinical practice. Then I lean back to the building the company. They're prioritizing it, having three priorities, having five priorities, and then being able to understand. And every company has some things which are similar, growth of your product development, continuing to advance the company, continuing to tell the story, attracting the right team members. It just gets magnified at a broader level. But the problems start similar, very similar. You know, think about when we talk about tech companies, Apple, the first thing they had to do, develop a product, then build a team, then sell the product, tell the, sell the vision, you know, and then continue to raise money. And that part is seems sometime very lonely. It also seems that I am uniquely burdened with these problems. And I always remind people, "You know, as much as you would like to think that you are unique. I assure you, it is not a problem that we are gifted with. We all have to face the same set of problems, sometimes more, sometimes less." So then you start to take them less personally. You start to say, "Okay, I'm not the first one to face this problem. These problems have happened to people like me before and they will overcome. How can I do it?" Then you'd become safe, a solution based thinking versus a place where you get overwhelmed with the problem because problems exist. And if anyone is listening to this podcast and if they've developed a started a company, I can assure you the problems come with a flood. They are not going to end ever. So it is disappointing. Sometime it feels that, "Oh my gosh, it is me versus the world," but it is not so. If you have good set of mentors, people who are not directly involved in day to day in your business, there are people who can help you think through it. And that is something that I find a great joy in talking to these CEOs, being able to help them understand the problem. And I say, you know, a couple of hours a month, but then when I go back to my own work, one that I realized this was the same problem I faced a few years ago. Two, it's a similar version of the problem I face at a slightly larger scale today. And three, being able to step out of from your own narrow zone, it gives you perspective. Then what I said to you about that problems are not, these are not personal problems. These are the problems we all face developing a product. It doesn't matter whether you healthcare. People tell me health care or product development is really hard. You talk to my colleagues, our CEOs who are running tech companies. Products in development and tech companies may seem easier, but to create a great product that truly solves customers problem, it's not easy. [00:30:30] Lindsey Dinneen: Yeah, and well, I love that mentorship and sort of teaching and guiding, giving advice to the next generation is something is of a core value of yours and something you really care about. And it actually is a great segue into my next question, which is just pivoting the conversation for fun, imagine that you were to be offered a million dollars to teach a masterclass on anything you want. It can be within your industry, what you're doing right now, but it doesn't have to be. What would you choose to teach? [00:31:02] Dr. Shalabh Gupta: I think as much as we all feel that entrepreneurship is an external game, I think it's a lot of internal mindset, being able to understand yourself better. Being able to understand who you are, what are your true core values, what really drives you. It takes time and it requires a continuous interrogation, asking yourself, "Is this really what I enjoy?" Some of us feel it's a glamour that we feel like we want to be CEO. Some of us would be better off as a CTO, Chief Technology Officer. Some of us would not want to do startups. It's not for everybody. And it's okay because you can work in a bigger company and can be, you know, people talk about entrepreneurial pursued within a large organization. Maybe that's what for you. But being able to understand yourself, it's a very important part. And I think unfortunately, formal education does not help us no matter what degrees and which schools. And it really doesn't matter whether you a science degree, MD, PhD, or your business school degree like MBA, we're all very uniquely different, and we have different values. What one person sees inspired by, for somebody else, it may be a nightmare, you know. It's a thing that people think that startups are so much fun. I read a joke. It says, "People leave 9 to 5 job to work from 5 to 9, which is 5 a. m. to 9 p. m." So I think that's because this is some truth to it. And I've said to people again and again that if making money is your objective, please don't go as to run a startup. It is probably the worst way to think about pursuing the financial part. You do something because you have a faith and belief in something. And it doesn't have to be the faith about changing humanity. It's about something that you have a unique skill set or unique product idea that you believe you can bring to the marketplace. The biggest focus we all can have is making an impact. If I can serve a large number of patients, I can serve a large physician, I will have a product that will make money, therefore, that will make money for enterprise that will make money for investors. And therefore, as a company, we will make money. It's a very simple truth, but we like to make it complicated. I really mean it. The more I got to understand this part of the process better, which goes back to the basic thing that I said to you, if you said that you have a master class, the one thing I will say to you, it's spend time to understand yourself. And it's okay to realize that what I thought I like, I don't like it. The part that I talked to you about flow, it takes efforts. I've had many careers, but when I work in my company, the time can stop for four or five hours, literally we can be working on something. And I have a team and it's not just me alone. I have a team that when we think about a problem, these are people who have spent three decades in working in different companies, large, small, many size companies, we could work cohesively, collectively, think about a problem. And that to me, it's a joy. For me, that is a creation, right? You know, we're thinking about the problem, which may be a design of a clinical trial, because we have to think we have to use brains. And I always say, "God gave us a gift, which is a neuron. So use it, let's use them." And challenge yourself, right? And the challenge in a good way, not be a condescending ending jerk and say "No, how could you do it?" I try to say to people, "Look, I understand this is how it is done, but I want to do two things. Number one, please believe me that we can do better, faster, cheaper. And number two, I promise you that whatever I'm telling you, I'm not going to tell you and walk out of the conference room. I will work hand to hand." We call it a hand to hand combat is essentially that I'm not just telling you I'm going to work with you. I want to find the solution, but we can't do that thing that are you used to. Every trial, people tell me it's going to take 18 months, 12 months, it's going to cost as much. We shrink that thing timeline cost by not 10, 20%. We talking 50%. And these are people have done this before. So, so I need the courage to be honest and say, "No, we can't do it. We have to do it faster, better, cheaper, but how?" And then asking them. So, I say, "It's okay that we walk away and we don't have a clue. It's okay. Today's Thursday. Let's come back. Take three days to think about it." But the reason is that because when you ask yourself from a place that I can't do it, the mind is start to find solution versus when you say, no, I can't do it. Because in that case, it's a subconscious mind that keeps on giving you 15 reasons why you can't do it. People talk about growth mindset. I've always said to people, "We may not be able to do this thing today, but the understanding that with a little bit of help, a little bit of patience, a little bit of it, making ourself better, we can become that company, we can become that organization." And that really requires challenging ourself. And that's where I went back to. I want to go back to this question you asked earlier. People talk a lot about entrepreneurship as if it is some very specific skill set. I think because if you know yourself, you know what is your true zone is, then you want to surround yourself places that you are either not good at, or you don't enjoy doing it, right? In the beginning, it is just you and a vast amount of problems to face. Then you start to build your team. Then you start to see yourself, "You know, maybe Bob can do this work. I really, I'm not that good at it. I don't like doing it." Then you start to rely and surround yourself with not same skill set, but the people who are complementary skill set. And that's how you build a team. That's the foundation of team. Then you build trust and you say to Bob, "Whatever you do, it's not your fault. I'm here to protect you." You don't point fingers at each other. We always remind the example of Navy SEAL. You know, I've never worked in the US Army. I was not an Army veteran, but the ethos that Navy SEAL uses where the team wins, I always tell people we are a winning team. We are not looking for MVPs, you know, because the teams win. Teams create products, teams create value. Individual glories is not useful and this is something you have to keep reminding us that we keep drilling it down and say " No, it's not Bob. It's not John. It's not James. It's us. It's as a team." Again, as you grow through the company stages, your skill set has to continue to evolve and people always say, "Well, how do you lead a team?" The first thing that I always said, "Every single person in my team, you are a leader. Why? You wake up in the morning, brush your teeth. You're leading yourself." Really! Like, what do you do with your day? If you happen to be a parent or partner, a spouse or somebody, you have people you influence around yourself, right? So instead of worrying about, "Oh, you know, I want to lead a company." First, you have to lead yourself and you have to lead with courage. It's starting a company, building a company, right? Yeah. No matter what the media tells you, it is hard. It's hard to develop a product. It's hard because the challenges are not one or two. There are many. Being able to drill down, saying "These are the three things I'll focus on. These are the only things that matter." And then if something new comes up, you have to face that challenge and put the third in your list. It comes in a different page. You know, I use this basic exercise. I have a notebook, a physical notebook and not electronic one, and a piece of paper. What are the top three priorities? And then the other part is that I've asked people to do this exercise when startup companies, CEOs come and tell me all their problems, all the things they want to do. I said, "Humor me if you will. This is the end of the year. And let's say today is we are in 2025. What would you like to tell yourself a year from now? If everything happened the best you could imagine, how many customers, how many products, what will be the stage of product, who would have funded you? Who are the people behind you?" And I asked him to write in a whiteboard. And I say, imagine, no, this is the five thing. If they write 25 things, I say, "No, this is down to five things. What are those five things you would like?" And again, everything has just gone and you can't believe you're sitting there. What will it take? Is it this? And then you start to have a goalpost, right? It's a target. Then you work backward. [00:39:37] Lindsey Dinneen: Yeah. Yeah. Well, that's great. That is such great advice. So thank you, first of all, for sharing, but I think in general, your masterclass would be so much-- you'd have to have a full day or more. That's great though. I love that. How would you wish to be remembered after you leave this world? [00:39:57] Dr. Shalabh Gupta: That's a very good question. That's one that I ask myself every day. The most important thing for me is to be who I am to make a difference for people who are around me. For me, my family is very important. I have kids and I always think about it. What will my children remember? Then it comes down to people who work with me. We want to give an experience to people. I've had people who have worked for I keep saying it two or three decades. My true wish is that I always say for whatever time they work at Unicycive, I want them to be remembering this is the best time they work for a company and that is the best hope we can do it. Because as a entrepreneur, if I can make our company the best experience, best environment, then that creates the best products. And a company like us, we realize that we are going to face challenges and it's not a question of this, the question is how many challenges. The question is not going to be, "Will the challenge defeat us?" The question is, "How do we overcome the challenges?" So it's about growth mindset, having a very distinct, clear vision and empowering people. And last thing is that what we do in healthcare affects millions of people people. Our drug is not going to be just in the U. S. We have partnerships outside U. S. We think about patients in China, South Korea, Southeast Asia. We are talking to companies in Europe. It's an opportunity to make a difference globally. And that is what keeps us going. That's what, you know, when that's when I talk with flow, that is what makes you want to work, whether it's a weekend or whether it's a late evening. And I think that is something which we all need to do to find something that is meaningful. And meaning means different things to different people in different phases of life. So it doesn't have to be, you know, I tell even my own team member, " Unicycive does not have to be the purpose of your life, but let me help you to manifest your best version so you can work well, because you are working here, you are spending your time, might as well make it meaningful for you and for the company." So finding that balance is key and it's a constant challenge. I never take anything for granted. It's a constant to my own team members. How can we make it better? You know, people always say the company grows and we started with the company. We went to IPO with one person. That was just me as an employee, which is not a common thing. I frankly don't know any other company that I've ever seen that went to a straight IPO with one employee. But that wasn't about me. It was about building the company, building the team. Today, we have 25 or so more, but it's still a small team. And people always ask me, "How do we go from 25 to 50 and it still remain the same." I said "Exactly how we became 5 to 10 to 15, 15 to 20." Because if you keep the culture same, focus same, and you remind people that it's not about who we are individually, but it's what we could be collectively. And you have it going and you know, something you're passionate about, you will give all that you got and then some more or else there is not worth fighting for because life is hard and building a product developing a technology or running a company is hard. So, either you are a full believer or else you can't do it. I mean, if you can do it, it's going to be miserable on both front. You want to do a good job and you will find it very difficult. So. [00:43:24] Lindsey Dinneen: Yeah. Indeed. Yeah. Excellent. Well, and then final question. What is one thing that makes you smile every time you see or think about it? [00:43:36] Dr. Shalabh Gupta: I think when you look back on the challenges that you once thought were unsurmountable, and then you say to yourself, "Huh, that was just a curve in the road, not a roadblock." Then you start to smile because of not because how smart you are, but how much together a team can accomplish. And you start to find, if you're working in a company setting, you start to feel that people start to feel empowered. My team says that you did it. I said, "No, we did it. I just showed you a judicious path, but you did it. I didn't do it. All I said to you is to change your framework." Because it's a framework. It's a mindset. And I keep saying about mindset because if you come with the idea that " No, I only, I need this much money, this much time, these many resources," you'll find you the subconscious mind keeps on validating those challenges. But if you say, "No, people like us have done it before I can do it, we can do it." And give them the time and space and say, "Look, you don't have to have an answer right now, but please go back and just think about it." Then they come back with the answer and they themselves surprised. But it truly requires a authenticity, a vulnerability, and being absolutely willing to fall on your face and get up and just fight again. And that's part people don't realize. People think about that every company is a smooth road up, but the companies go through the cycle. It's not when you're going up, it's what happens when you fall down. Can you pick yourself up? And it's not just with your team, but with your investors too. You know, we thought that we're going to file an NDA in 2020. You know, 2024, we had planned for everything and the whole thing was there, but we ended up in having to run an additional trial and then you have to communicate with integrity through transparency. This is what happened. This is what is there, but we can accomplish that. So then that all of all that helps you to look back a smile, laugh and say, "Okay, I accomplished that. We can do the next one." And that keeps the growth happening. And at the end of the day, we are not happy because we accomplished small things by doing small effort. Most of us as human beings want to be challenged in the right way and we feel joy in doing hard things that take a lot of efforts and once seemed just impossible to do it. And the question is, can you do it with your entire team, not just personally? And that's what inspires people. We want to be that company that people want to work for not because they need a job, not because we can take care of their 401k. I mean, those are a wonderful thing and I'm blessed that we can do all of that, because once upon a time, we didn't have any of that. So I don't take it for granted, it is something. But the fact is that what was the mission hasn't changed ever. And you know, that that is something which is worth pursuing it. And I think if people start to see that they can accomplish that, these challenges are not personal, that they are bound to come. And then they have a support group, you know, we all need somebody other than ourselves and people whom we are surrounded with somebody to hold our hand and say no, you fell down, but it's okay. You can get up. I think it's that support system, right? The more you can have it, the more different types of people you can relate to and call them friends, mentors, that helps. And I have tons and tons of them because my gosh, I mean, there are days seems like, how would I ever get out of this? As much as you may think that I have all the source of inspiration, but then if somebody else holds your hand, they say, no, you can do it. That is what gets you going to the next step. [00:47:25] Lindsey Dinneen: Absolutely. Well, goodness, this has been an amazing conversation, just packed full of incredible, helpful advice, and just very practical down to earth sharing. So thank you so much for your time today. I really appreciate everything you're doing to, to make an impact. So thanks again for your time. [00:47:44] Dr. Shalabh Gupta: Thank you very much. Thank you for hosting me and thank you for your time and interest. Really appreciate it. [00:47:49] Lindsey Dinneen: Of course. We are so honored to be making a donation on your behalf today to Feeding America, which works to end hunger in the United States by partnering with food banks, food pantries, and local food programs to bring food to people facing hunger. And also they advocate for policies that create long term solutions to hunger. So thank you so much for choosing that charity to support, and we just wish you the most continued success as you work to change lives for a better world. And thank you also to our listeners for tuning in. And if you're feeling as inspired as I am right now, I'd love it if you'd share this episode with a colleague or two, and we will catch you next time. [00:48:31] Ben Trombold: The Leading Difference is brought to you by Velentium. Velentium is a full-service CDMO with 100% in-house capability to design, develop, and manufacture medical devices from class two wearables to class three active implantable medical devices. Velentium specializes in active implantables, leads, programmers, and accessories across a wide range of indications, such as neuromodulation, deep brain stimulation, cardiac management, and diabetes management. Velentium's core competencies include electrical, firmware, and mechanical design, mobile apps, embedded cybersecurity, human factors and usability, automated test systems, systems engineering, and contract manufacturing. Velentium works with clients worldwide, from startups seeking funding to established Fortune 100 companies. Visit velentium.com to explore your next step in medical device development.

Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.## Intellia reported an adverse event in its gene therapy trial, causing its stock to drop, adding to existing safety concerns in gene therapy. Analysts downplayed the event, but patient deaths in other trials have raised red flags.## Moderna lost a $760 million bird flu vaccine contract amid uncertainties surrounding its COVID-19 vaccine. ## Other news includes Iteos closing down after a failed trial, Merck and Daiichi Sankyo pulling a lung cancer filing, and Novo opposing pharma tariffs.## AGC Biologics will be at Bio International to discuss their capabilities in drug production. ## Additional stories cover Rocket's gene therapy hold, Biogen's strategy shift, and AbbVie's staff cuts.

This week's episode of The PR Week podcast comes to you from PRWeek's Women of Distinction event at The Lighthouse at Pier 61 in New York City.PRWeek's associate news editor Diana Bradley and reporter Julia Walker discuss this year's Women of Distinction and Women to Watch honorees. Additionally, they give highlights from a panel held with comms execs from Wendy's, McDonald's and Merck on coping with RTO mandates as moms and a talk with Baked by Melissa CEO and cofounder Melissa Ben-Ishay.The episode also includes conversations with honorees from on and off the stage at the event. Follow us: @PRWeekUSReceive the latest industry news, insights, and special reports. Start Your Free 1-Month Trial Subscription To PRWeek

The 2017 NotPetya cyberattack remains one of the most devastating and costly breaches in history, inflicting over $1.4 billion in damages on pharmaceutical giant Merck. What made this attack especially alarming was its simplicity: a single overprivileged service account became the key that unlocked chaos across Merck's global network. In episode 74 of the Hybrid Identity Protection Podcast, host Sean Deuby sits down with Lance Peterman, CIDPRO, who was on the front lines during the breach. Lance shares a rare, firsthand account of how the attack unfolded, the critical identity vulnerabilities that were exploited, and the long road to recovery.

00:03:50 - 00:18:12Trump's $175 billion Golden Dome missile defense system aims to use space-based interceptors to counter advanced missiles, but China warns it risks militarizing space and sparking an arms race. Congress estimates costs at $500 billion over 20 years. Russia's nuclear-powered Burevestnik missile, with unlimited range, could render it obsolete, raising concerns about budget overruns and SpaceX's involvement. 00:18:36 - 00:26:10Neocons push for war with Iran, demanding its nuclear program's dismantlement, while MAGA influencers like Bannon and Greene favor diplomacy. This reflects public exhaustion with Middle East wars, opposing defense contractors' agendas, with the host noting a hopeful shift against escalation. 00:31:12 - 00:38:12The Pentagon, citing unverified Chinese “super soldier” claims, proposes genetic experiments on U.S. troops using CRISPR and mRNA, alongside biosurveillance. Ethical concerns arise over human experimentation and CIA ties, with deregulation favoring biotech firms, risking taxpayer funds and safety. 00:44:45 - 00:53:36Trump grants asylum to 54 Afrikaner South Africans facing violence and land confiscation, confronting Ramaphosa with evidence of “white genocide.” The host supports this, criticizing media deflections and narrow refugee definitions, emphasizing the severe persecution Afrikaners endure. 01:17:37 - 01:36:07The FDA now requires trials for COVID-19 vaccines for healthy people aged 6 months to 64, but approved high-risk group vaccines without data, rushed by Trump's “warp speed.” A Senate report reveals Biden officials hid myocarditis risks in young men, delaying warnings despite early signals, driven by corporate interests. Low vaccine uptake (13% kids, 23% adults) and rising heart issues highlight the cover-up. 01:36:07 - 01:40:50Medpage Today confirms RFK Jr.'s claim that the MMR mumps vaccine is ineffective, admitting Merck's fraudulent data, but dismisses him as a lawyer. Failed lawsuits left untested, harmful vaccines on the market, with one-third of trial kids facing health issues, exposing systemic vaccine regulation flaws. 01:48:10 - 02:01:35A bill strips states' AI regulation rights for 10 years, a Trump-backed federal power grab seen as unconstitutional. States urged to block AI infrastructure. Vermont pauses its EV mandate, citing weak tech and infrastructure, resisting California's 2035 EV push, which could set a national standard. 02:04:03 - 02:08:48Rep. Luna's bill seeks to repeal the Patriot Act, blamed for post-9/11 surveillance and rights violations. The host sees 9/11 as a pretext for wars and a police state, urging the act's end to curb intelligence agency abuses and restore privacy. 02:10:21 - 02:34:23Cecile Richards, dead at 67 from brain cancer, is condemned for leading 3.5 million abortions at Planned Parenthood and alleged fetal part sales. Her unrepentant stance, Freedom from Religion awards, and Biden's Medal of Freedom are criticized as anti-God. Kushner's 2017 funding offer was rejected. Abortion's 2024 toll (45.1 million, 42% of deaths) and 60% of African American deaths are called “black genocide.” GOP's funding via CARES Act ($80 million) and MAGA's defense of Trump's vaccines are slammed. 02:37:05 - 02:49:03Brown Foods' “Unreal Milk” and Israeli lab-grown dairy, like Wilk, claim to cut emissions by 82%, backed by Gates and USDA despite no farming. Biomilq targets infants, tied to C40's no-dairy push. Called “tumor milk,” it's criticized as an anti-agriculture, climate-driven scam with lax FDA oversight. 02:50:39 - 03:00:36Trump's “Gold Card” visa, costing $5 million, claims 250,000 applicants to raise $1 trillion, but only 277,000 global millionaires qualify. Offering tax-free foreign income and no country caps, it's decried as a corrupt deal for Trump's allies, bypassing vetting and America-first values.Follow the show on Kick and watch live every weekday 9:00am EST – 12:00pm EST https://kick.com/davidknightshow Money should have intrinsic value AND transactional privacy: Go to https://davidknight.gold/ for great deals on physical gold/silver For 10% off Gerald Celente's prescient Trends Journal, go to https://trendsjournal.com/ and enter the code KNIGHT Find out more about the show and where you can watch it at TheDavidKnightShow.comIf you would like to support the show and our family please consider subscribing monthly here: SubscribeStar https://www.subscribestar.com/the-david-knight-showOr you can send a donation throughMail: David Knight POB 994 Kodak, TN 37764Zelle: @DavidKnightShow@protonmail.comCash App at: $davidknightshowBTC to: bc1qkuec29hkuye4xse9unh7nptvu3y9qmv24vanh7Become a supporter of this podcast: https://www.spreaker.com/podcast/the-david-knight-show--2653468/support.

00:03:50 - 00:18:12Trump's $175 billion Golden Dome missile defense system aims to use space-based interceptors to counter advanced missiles, but China warns it risks militarizing space and sparking an arms race. Congress estimates costs at $500 billion over 20 years. Russia's nuclear-powered Burevestnik missile, with unlimited range, could render it obsolete, raising concerns about budget overruns and SpaceX's involvement. 00:18:36 - 00:26:10Neocons push for war with Iran, demanding its nuclear program's dismantlement, while MAGA influencers like Bannon and Greene favor diplomacy. This reflects public exhaustion with Middle East wars, opposing defense contractors' agendas, with the host noting a hopeful shift against escalation. 00:31:12 - 00:38:12The Pentagon, citing unverified Chinese “super soldier” claims, proposes genetic experiments on U.S. troops using CRISPR and mRNA, alongside biosurveillance. Ethical concerns arise over human experimentation and CIA ties, with deregulation favoring biotech firms, risking taxpayer funds and safety. 00:44:45 - 00:53:36Trump grants asylum to 54 Afrikaner South Africans facing violence and land confiscation, confronting Ramaphosa with evidence of “white genocide.” The host supports this, criticizing media deflections and narrow refugee definitions, emphasizing the severe persecution Afrikaners endure. 01:17:37 - 01:36:07The FDA now requires trials for COVID-19 vaccines for healthy people aged 6 months to 64, but approved high-risk group vaccines without data, rushed by Trump's “warp speed.” A Senate report reveals Biden officials hid myocarditis risks in young men, delaying warnings despite early signals, driven by corporate interests. Low vaccine uptake (13% kids, 23% adults) and rising heart issues highlight the cover-up. 01:36:07 - 01:40:50Medpage Today confirms RFK Jr.'s claim that the MMR mumps vaccine is ineffective, admitting Merck's fraudulent data, but dismisses him as a lawyer. Failed lawsuits left untested, harmful vaccines on the market, with one-third of trial kids facing health issues, exposing systemic vaccine regulation flaws. 01:48:10 - 02:01:35A bill strips states' AI regulation rights for 10 years, a Trump-backed federal power grab seen as unconstitutional. States urged to block AI infrastructure. Vermont pauses its EV mandate, citing weak tech and infrastructure, resisting California's 2035 EV push, which could set a national standard. 02:04:03 - 02:08:48Rep. Luna's bill seeks to repeal the Patriot Act, blamed for post-9/11 surveillance and rights violations. The host sees 9/11 as a pretext for wars and a police state, urging the act's end to curb intelligence agency abuses and restore privacy. 02:10:21 - 02:34:23Cecile Richards, dead at 67 from brain cancer, is condemned for leading 3.5 million abortions at Planned Parenthood and alleged fetal part sales. Her unrepentant stance, Freedom from Religion awards, and Biden's Medal of Freedom are criticized as anti-God. Kushner's 2017 funding offer was rejected. Abortion's 2024 toll (45.1 million, 42% of deaths) and 60% of African American deaths are called “black genocide.” GOP's funding via CARES Act ($80 million) and MAGA's defense of Trump's vaccines are slammed. 02:37:05 - 02:49:03Brown Foods' “Unreal Milk” and Israeli lab-grown dairy, like Wilk, claim to cut emissions by 82%, backed by Gates and USDA despite no farming. Biomilq targets infants, tied to C40's no-dairy push. Called “tumor milk,” it's criticized as an anti-agriculture, climate-driven scam with lax FDA oversight. 02:50:39 - 03:00:36Trump's “Gold Card” visa, costing $5 million, claims 250,000 applicants to raise $1 trillion, but only 277,000 global millionaires qualify. Offering tax-free foreign income and no country caps, it's decried as a corrupt deal for Trump's allies, bypassing vetting and America-first values.Follow the show on Kick and watch live every weekday 9:00am EST – 12:00pm EST https://kick.com/davidknightshow Money should have intrinsic value AND transactional privacy: Go to https://davidknight.gold/ for great deals on physical gold/silver For 10% off Gerald Celente's prescient Trends Journal, go to https://trendsjournal.com/ and enter the code KNIGHT Find out more about the show and where you can watch it at TheDavidKnightShow.comIf you would like to support the show and our family please consider subscribing monthly here: SubscribeStar https://www.subscribestar.com/the-david-knight-showOr you can send a donation throughMail: David Knight POB 994 Kodak, TN 37764Zelle: @DavidKnightShow@protonmail.comCash App at: $davidknightshowBTC to: bc1qkuec29hkuye4xse9unh7nptvu3y9qmv24vanh7Become a supporter of this podcast: https://www.spreaker.com/podcast/the-real-david-knight-show--5282736/support.

In this episode, we meet Dr. Sandy Robertson, currently a Chemistry Teacher and STEMBlazers Moderator at Regis Jesuit High School and former Director of Global Pharmaceutical Development and Commercialization at Merck & Co.

This featured podcast includes a discussion with 3 experts on managing patients with hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer (mBC) from a satellite symposium held in conjunction with the 42nd Annual Miami Breast Cancer Conference® in March 2025. In observational studies of treatment patterns in older women with mBC, approximately half of the patients were undertreated, and only half received a CDK4/6 inhibitor (CDK4/6i)-based regimen in the first-line setting. Reasons for undertreatment include concerns about the patient's age, perceived frailty, and underlying health issues. Aging is a heterogeneous process; older patients must receive individualized treatment that is not based solely on their age but on a comprehensive assessment that objectively assesses their overall health and ability to tolerate treatment. This program is designed to help clinicians assess the fitness of older patients with HR+/HER2– mBC, review the efficacy and safety of CDK4/6i in this patient population, and individualize treatment decision-making appropriately. Acknowledgment of Educational Grant Support This activity is supported by an educational grant from Pfizer Inc. Today's faculty are: Hope S. Rugo, MD Director, Women's Cancers Program Division Chief, Breast Medical Oncology Professor, Department of Medical Oncology & Therapeutics Research City of Hope Comprehensive Cancer Center Duarte, CA Professor Emeritus, UCSF Disclosures: Grant/Research Support: Ambrx; AstraZeneca; Daiichi Sankyo, Inc; F. Hoffmann-La Roche AG/Genentech, Inc; Gilead Sciences, Inc; Lilly; Merck & Co., Inc; Novartis Pharmaceuticals Corporation; OBI Pharma; Pfizer; Stemline Therapeutics. Consultant: Napo Therapeutics; Puma Biotechnology; Sanofi. Honoraria: Chugai; Mylan/Viatris. Neil M. Iyengar, MD Associate Attending, Breast Medicine Service Program Lead, MSK Healthy Living Department of Medicine Memorial Sloan Kettering Cancer Center Associate Professor of Medicine Weill Cornell Medical College New York, NY Disclosures: Consultant/Adviser: Arvinas, AstraZeneca, BD Life Sciences, Daiichi Sankyo, Genentech/Roche, Gilead, Menarini-Stemline, Novartis, Pfizer, Puma, Seagen, TerSera Therapeutics. Speaker: Cardinal Health, Curio Sciences, DAVA Oncology, IntrinsiQ Health. Editorial Position: npj Breast Cancer, Oncology®. Equity/Ownership: Complement Theory, Bettering Company. Research Support (to institution): American Cancer Society, Breast Cancer Research Foundation, Conquer Cancer Foundation, Kat's Ribbon of Hope, National Cancer Institute/National Institutes of Health. Contracted Research: Novartis, SynDevRx. Komal Jhaveri, MD, FACP Patricia and James Cayne Chair for Junior Faculty Associate Attending Physician, Breast Medicine Service and Early Drug Development Service Section Head, Endocrine Therapy Research Program Clinical Director, Early Drug Development Service Memorial Sloan Kettering Cancer Center Associate Professor of Clinical Medicine Weill Cornell Medical College New York, NY Disclosures: Consultant/Advisory Board: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo Inc, Eisai Inc, Genentech, a member of the Roche Group, Gilead Sciences Inc, Jounce Therapeutics, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Menarini Group, Novartis, Olema Oncology, Pfizer Inc, Scorpion Therapeutics, Seagen Inc, Stemline Therapeutics Inc, Sun Pharma Advanced Research Company Ltd, Taiho Oncology Inc. Research Funding: AstraZeneca Pharmaceuticals LP, Debiopharm, Genentech, a member of the Roche Group, Gilead Sciences Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Novartis, Pfizer Inc, Puma Biotechnology Inc, Scorpion Therapeutics, Zymeworks Inc. The staff of Physicians' Education Resource®, LLC, have no relevant financial relationships with ineligible companies. PER® mitigated all COI for faculty, staff, and planners prior to the start of this activity by using a multistep process. Off-Label Disclosure and Disclaimer This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this accredited activity is for continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient's medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or any company that provided commercial support for this activity.

Send us a textIn this episode, Tiago Matos, Associate Principal Scientist/Associate Director in Bioprocess Drug Substance and Commercialization at Merck & Co., shares a critical insight: continuous manufacturing in biologics currently demands 2–3x more time and FTEs than traditional fed-batch approaches. This highlights both the complexity of the shift - and the urgency for smarter digital tools and cross-functional collaboration.With over a decade of experience and a strong track record in biologics and smart manufacturing, Tiago brings a balanced view of the promise and practical challenges of digital transformation in bioprocessing.Top 3 Takeaways:Continuous Manufacturing is Coming - But Slowly: The infrastructure and tools aren't fully ready. Progress depends on better-integrated solutions and stronger collaboration across industry, equipment providers, and regulators.Collaboration is Key: No one drives transformation alone. Digital, automation, modeling, and process experts must work together - like building a functional protein from diverse amino acids.Digital Twins and AI Will Bridge the Gap: AI, soft sensors, and digital twins will help streamline control strategies. The goal isn't perfect models, but reliable, adaptive systems that improve in real time.Tiago's vision is both realistic and inspiring: the future of biologics manufacturing lies in openness, teamwork, and continuous learning.What challenges or questions do you face in the shift to digital bioprocessing?Here is what other guests had to say on this topic:Episodes 5-6: Hybrid Modeling: The Key to Smarter Bioprocessing with Michael Sokolov;Episodes 85-86: Bioprocess 4.0: Integrated Continuous Biomanufacturing with Massimo Morbidelli;Episodes 121-122: The Transformative World of Digital Solutions in Bioprocessing with Simon Wieninger.Connect with Tiago Matos:LinkedIn: www.linkedin.com/in/tiagobmatosMerck & Co.: www.merck.comNext step:Transform your bioprocess development strategy with a complimentary consultation. Schedule your expert session: https://bruehlmann-consulting.com/callReady to scale up? Join our exclusive 1:1 Strategy Call and learn proven methods to reduce development and manufacturing costs while maintaining product quality. Our bioprocess experts will help you navigate complex bioprocessing challenges and regulatory requirements. Limited spots available: https://stan.store/SmartBiotech

In this podcast episode, Ryan Stidham, MD, discusses the evolution and development of digital imaging and AI in the GI space, how AI can revolutionize stages within the clinical trials and practices and more. •    Intro :24 •    The interview/about Stidham :36 •    Tell us about your family and where you grew up. 1:14 •    How did you embrace changes in technology growing up? 3:07 •    What was the seminal moment that got you to move from being a consumer of information to being a producer and innovator?  6:05 •    What ignited you to start commercializing and patenting your ideas, and operationalizing them into a company? How did that evolution occur? 8:32 •    Can you give a quick overview of what these tools and technologies entail?  12:52 •    What got you interested in inflammatory bowel disease, and how did your childhood interest in coding shift to artificial intelligence? 18:12 •    Where did your interest in AI come about? 20:26 •    You recently published a review on how AI will revolutionize the conduct of clinical trials in inflammatory bowel disease […] Will AI remove the need for central reading in IBD trials in the future? 23:58 •    How do we change the way we train GI doctors, and should we start making these changes today? 26:38 •    With AI rapidly changing the landscape, are we spending enough time educating our fellows in how to adapt to changes and communicate with patients? 32:33 •    What do you think will change in IBD and gastroenterology in the near term as a result of AI? 35:06 •    What is it that we really need in terms of health care access, and how can AI technology assist these needs? 38:39 •    Thank you, Ryan 44:04 •    Thanks for listening 44:20 Ryan Stidham, MD, MS, AGAF, is a translational scientist caring exclusively for patients with inflammatory bowel disease. He is an associate professor in the department of medicine and the department of computational medicine and bioinformatics where he serves as the associate chair of translational research. His research focus is the use of artificial intelligence to improving measurement of IBD and other gastrointestinal diseases, developing new interpretations of cross-sectional imaging, endoscopy, medical text, and other electronic data.  We'd love to hear from you! Send your comments/questions to guttalkpodcast@healio.com. Follow us on X @HealioGastro @sameerkberry @umfoodoc. For more from Stidham, follow @CrohnsDoc on X. Disclosures: Berry and Chey report no relevant financial disclosures. Stidham reports consulting or on advisory boards for AbbVie, Bristol Myers Squibb, CorEvitas, Eli Lilly, Exact Sciences, Gilead, Janssen, Merck, Pfizer, and Takeda. Stidham holds intellectual property and equity on medical imaging and endoscopic analysis technologies licensed by the University of Michigan to PreNovo, LLC, AMI, LLC and PathwaysGI, Inc.

This Oncology PER®Spectives™ podcast explores the role of EZH2 in metastatic castration-resistant prostate cancer (mCRPC) progression and its synergy with androgen receptor inhibitors. In this podcast, experts Neeraj Agarwal, MD, FASCO; Himisha Beltran, MD; and Maha Hussain, MD, FACP, FASCO, discuss the management of mCRPC. Acknowledgment of Educational Grant Support This activity is supported by an educational grant from Pfizer Inc. Accreditation/Credit Designation Physicians' Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Physicians' Education Resource®, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians' Education Resource®, LLC is approved by the California Board of Registered Nursing, Provider #16669, for 1.5 Contact Hours. Instructions on How to Receive Credit Listen to this podcast in its entirety. Go to gotoper.com/credit and enter code: 6947 Answer the evaluation questions. Request credit using the drop-down menu. You may immediately download your certificate. Today's faculty are: Neeraj Agarwal, MD, FASCO Professor of Medicine Senior Director for Clinical Research HCI Presidential Endowed Chair of Cancer Research Director, Center of Investigational Therapeutics Director, Genitourinary Oncology Program Huntsman Cancer Institute, University of Utah (NCI-CCC) Salt Lake City, UT Disclosures: Grant/Research Support (paid to institution): Arvinas, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, GlaxoSmithKline, Immunomedics, Janssen, Lava, Merck, Nektar, Neoleukin, Novartis, Oric, Pfizer, Roche, Sanofi, Seagen, Takeda, Tra-con Himisha Beltran, MD Associate Professor of Medicine Director of Translational Research Within Medical Oncology Harvard Medical School Lank Center for Genitourinary Oncology and the Division of Molecular and Cellular Oncology Dana Farber Cancer Institute Boston, MA Disclosures: Grant/Research Support: Circle Pharma, Daiichi Sankyo, Novartis; Adviser: Amgen, AstraZeneca, Daiichi Sankyo, Novartis Maha Hussain, MD, FACP, FASCO Genevieve E. Teuton Professor of Medicine Professor, Medicine (Hematology/Oncology) Deputy Director Robert H. Lurie Comprehensive Cancer Center Northwestern University Feinberg School of Medicine Chicago, IL Disclosures: Advisory Board: AstraZeneca, Bayer, Convergent Therapeutics, Honoraria: AstraZeneca, Bayer The staff of Physicians' Education Resource®, LLC, have no relevant financial relationships with ineligible companies. PER® mitigated all COI for faculty, staff, and planners prior to the start of this activity by using a multistep process. Off-Label Disclosure and Disclaimer This activity may or may not discuss investigational, unapproved, or off-label use of drugs. Learners are advised to consult prescribing information for any products discussed. The information provided in this accredited activity is for continuing education purposes only and is not meant to substitute for the independent clinical judgment of a health care professional relative to diagnostic, treatment, or management options for a specific patient's medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or any company that provided commercial support for this activity. Release Date May 14, 2025 Expiration Date May 14, 2026

Send us a textAs the biotechnology sector races toward digital transformation, the buzz around Industry 4.0 - with its promise of interconnected systems, automation, and data-driven operations - has never been louder. But is the industry truly ready?In this episode, we speak with Tiago Matos, Associate Principal Scientist/Associate Director in Bioprocess Drug Substance and Commercialization at Merck & Co., who brings a grounded, insider view. Despite the hype, he says most of biopharma is still operating at an “Industry 3.2” level.With over a decade of experience in biologics and vaccines, Tiago leads teams pushing digital innovation forward - through tools like digital twins, advanced control strategies, and smart manufacturing platforms.Key takeaways from this episode:Biotech is slowly transitioning toward true Industry 4.0, through collaboration and strategic leadership.Digital twins aren't for everything. Focused use in platform processes yields the best return - broad implementation can be costly and complex.Regulators are ready. Far from being a barrier, they're encouraging innovation and open to new ideas.Curious to learn more? Check out the full blog post for deeper insights, and let us know your thoughts in the comments - how close do you think biomanufacturing is to a true digital revolution?Here is what other guests had to say on this topic:Episodes 5-6: Hybrid Modeling: The Key to Smarter Bioprocessing with Michael Sokolov;Episodes 85-86: Bioprocess 4.0: Integrated Continuous Biomanufacturing with Massimo Morbidelli;Episodes 121-122: The Transformative World of Digital Solutions in Bioprocessing with Simon Wieninger.Connect with Tiago Matos:LinkedIn: www.linkedin.com/in/tiagobmatosMerck & Co.: www.merck.comNext step:Transform your bioprocess development strategy with a complimentary consultation. Schedule your expert session: https://bruehlmann-consulting.com/callReady to scale up? Join our exclusive 1:1 Strategy Call and learn proven methods to reduce development and manufacturing costs while maintaining product quality. Our bioprocess experts will help you navigate complex bioprocessing challenges and regulatory requirements. Limited spots available: https://stan.store/SmartBiotech